Publikationen von Prof. Jeltsch

Vollständige Liste und Auswahl an besonderen Veröffentlichungen

Highlights

Ab 2015

Adam et al. (2020) DNA sequence-dependent activity and base flipping mechanisms of DNMT1 regulate genome-wide DNA methylation. Nat Commun. 11:3723

DNA methylation on CG sequences is a chemical modification of DNA that is essential for human embryonic development. The DNA methyltransferase DNMT1 plays a central role in this process. The enzyme uses a spectacular base flipping mechanism, the basics of which are not well understood. An international research team led by Prof. Albert Jeltsch from the Institute for Biochemistry and Technical Biochemistry (IBTB) at the University of Stuttgart used biochemical and structural biological experiments to clarify the dynamic processes involved in this process.

In 1993 it was shown for the first time that DNA methyltransferases partially destroy the DNA double helix structure discovered by Watson and Crick in 1953 in the course of their catalyzed reaction, because the cytosine base to be methylated is flipped out of the DNA helix. The guanine, originally forming a base pair with the cytosine, is left behind in the DNA helix, which leads to dynamic structural changes in the DNA, which, however, have not yet been systematically investigated.

A team led by Prof. Albert Jeltsch from the University of Stuttgart was able to measure the DNA methylation rate of DNMT1 methyltransferase on thousands of DNA sequences containing CG target sequences using a new method. It was shown that the sequence environment has a significant influence on the enzyme activity. In cooperation with a group from the University of California, structures of DNMT1 with different DNA sequences could be solved, which show that the structural changes of the DNA after base flipping depend directly on the neighboring DNA sequence, and these effects also control the turnover rate of DNMT1 . Complexes with minor structural changes showed a high turnover rate, while a complex with a massive structure change showed a slow turnover rate.

With the help of modeling experiments and simulations in cooperation with the group of Prof. Radde from the University of Stuttgart, the mechanism of the reaction could be described in more detail. Further experiments showed that the DNA methylation pattern in human cells and also the effect of DNMT inhibitors used in cancer treatment are strongly influenced by the sequence dependence of DNMT1 activity. "It is fascinating to see how dynamic processes in biomolecules at the atomic level are reflected in global properties such as genome-wide DNA methylation patterns in human cells and the effects of drugs," says Jeltsch.

Link

Gao et al.  (2020) Comprehensive Structure-Function Characterization of DNMT3B and DNMT3A Reveals Distinctive De Novo DNA Methylation Mechanisms. Nat Commun. 11:3355

In the course of the evolution of higher organisms such as mammals, gene duplication often occurs. The resulting "twin genes" have a very similar genetic makeup, but are independent of each other and can therefore specialize in certain tasks. An example of this is DNA methylation, a chemical change in the basic building blocks of the genetic material of a cell, which is caused by the transfer of methyl groups by enzymes (DNA methyl transferases, DNMT) to certain locations in the DNA. The DNA-methyltransferases DNMT3A and DNMT3B are two forms of these enzymes in human cells that have arisen from gene duplication.

Over 20 years ago, it was discovered that DNMT3B is essential for the DNA methylation of certain regions in the human genome and that insufficient activity of DNMT3B leads to the so-called ICF syndrome. However, why DNMT3B is specifically required for this task and why, for example, the twin DNMT3A cannot take over this task has so far remained unknown.

DNMT3B is required for the methylation of certain sequences in human chromosomes (orange). The specificity of DNMT3B for these regions is determined by a specific protein loop around Arginine 823 (gray). Figure: University of Stuttgart / IBTB

In cooperation with groups from the University of California and the University of North Carolina at Chapel Hill, our team has now been able to solve the structure of DNMT3B in complex with other DNA sequences and measure the turnover rate of DNA methylation by DNMT3B and DNMT3A on thousands of DNA sequences. It was shown that DNMT3B is particularly active on its target sequences in the human genome due to a special protein loop, while DNMT3A can only work poorly on these sequences.

Link

Hofacker, Broche, Laistner, Adam, Bashtrykov & Jeltsch (2020) Engineering of Effector Domains for Targeted DNA Methylation with Reduced Off-Target Effects. Int J Mol Sci. 21(2)

Epigenome editing is a promising technology, potentially allowing the stable reprogramming of gene expression profiles without alteration of the DNA sequence. Targeted DNA methylation has been successfully documented by many groups for silencing selected genes, but recent publications have raised concerns regarding its specificity. In the current work, we developed new EpiEditors for programmable DNA methylation in cells with a high efficiency and improved specificity. First, we demonstrated that the catalytically deactivated Cas9 protein (dCas9)-SunTag scaffold, which has been used earlier for signal amplification, can be combined with the DNMT3A-DNMT3L single-chain effector domain, allowing for a strong methylation at the target genomic locus. We demonstrated that off-target activity of this system is mainly due to untargeted freely diffusing DNMT3A-DNMT3L subunits. Therefore, we generated several DNMT3A-DNMT3L variants containing mutations in the DNMT3A part, which reduced their endogenous DNA binding. We analyzed the genome-wide DNA methylation of selected variants and confirmed a striking reduction of untargeted methylation, most pronounced for the R887E mutant. For all potential applications of targeted DNA methylation, the efficiency and specificity of the treatment are the key factors. By developing highly active targeted methylation systems with strongly improved specificity, our work contributes to future applications of this approach.

Link

Emperle et al.  (2019) Mutations of R882 change flanking sequence preferences of the DNA methyltransferase DNMT3A and cellular methylation patterns. Nucleic Acids Res. 47(21):11355-11367

Somatic DNMT3A mutations at R882 are frequently observed in AML patients including the very abundant R882H, but also R882C, R882P and R882S. Using deep enzymology, we show here that DNMT3A-R882H has more than 70-fold altered flanking sequence preferences when compared with wildtype DNMT3A. The R882H flanking sequence preferences mainly differ on the 3' side of the CpG site, where they resemble DNMT3B, while 5' flanking sequence preferences resemble wildtype DNMT3A, indicating that R882H behaves like a DNMT3A/DNMT3B chimera. Investigation of the activity and flanking sequence preferences of other mutations of R882 revealed that they cause similar effects. Bioinformatic analyses of genomic methylation patterns focusing on flanking sequence effects after expression of wildtype DNMT3A and R882H in human cells revealed that genomic methylation patterns reflect the details of the altered flanking sequence preferences of R882H. Concordantly, R882H specific hypermethylation in AML patients was strongly correlated with the R882H flanking sequence preferences. R882H specific DNA hypermethylation events in AML patients were accompanied by R882H specific mis-regulation of several genes with strong cancer connection, which are potential downstream targets of R882H. In conclusion, our data provide novel and detailed mechanistic understanding of the pathogenic mechanism of the DNMT3A R882H somatic cancer mutation.

Link

Emperle et al. (2018) The DNMT3A R882H mutant displays altered flanking sequence preferences. Nucleic Acids Res. 46(6):3130-3139

Several recent studies reported that the R882H mutation in the DNMT3A DNA methyltransferase occurs frequently in AML and it has an early role in tumorigenesis, but its exact tumor promoting mechanism is not known. DNMT3A methylates DNA at CG sites, but its activity is strongly dependent on the surrounding DNA sequence context. In this work we show that the R882H mutation causes a pronounced shift in the flanking sequence preferences of DNMT3A, indicating that some CG sites are very poorly methylated by the mutant, while others are methylated even better by the mutant than by wildtype. Our data expand the model of the potential carcinogenic effect of the R882H mutation by showing CpG site specific activity changes. This result suggests that R882 is involved in contacts of DNMT3A to the DNA backbone, which mediate an indirect readout of flanking sequence preferences. This finding may explain the particular enrichment of the R882H mutation in cancer patients.

 

Link

Jurkowska et al. (2018) H3K14ac is linked to methylation of H3K9 by the triple Tudor domain of SETDB1. Nat Commun. 8(1):2057

SETDB1 is a histone methyltransferase that generates H3K9me3 marks in euchromatic regions. Here we show that the triple Tudor domain of SETDB1 binds histone H3 tails containing K14 acetylation combined with K9 methylation, and that the K9me/K14ac modification defines a novel bivalent chromatin state. Structural analyses revealed that peptide binding and K14ac recognition occurs at the interface between Tudor domains 2 and 3. Strikingly, a pocket switch mechanism was observed, because K9me1 or K9me2 is preferentially recognized by the aromatic cage of TD3, while K9me3 selectively binds to TD2. Genomic analyses show that K9me3/K14ac is enriched at SETDB1 binding sites overlapping with LINE elements, suggesting that recruitment of the SETDB1 complex to K14ac/K9me regions has a role in silencing of active genomic regions.

Link

Lungu et al. (2017) Modular fluorescence complementation sensors for live cell detection of epigenetic signals at endogenous genomic sites. Nature Communications 8:649

Investigation of the fundamental role of epigenetic processes requires methods for the locus-specific detection of epigenetic modifications in living cells. Here, we address this urgent demand by developing four modular fluorescence complementation-based epigenetic biosensors for live-cell microscopy applications. These tools combine engineered DNA-binding proteins with domains recognizing defined epigenetic marks, both fused to non-fluorescent fragments of a fluorescent protein. The presence of the epigenetic mark at the target DNA sequence leads to the reconstitution of a functional fluorophore. With this approach, we could for the first time directly detect DNA methylation and histone 3 lysine 9 trimethylation at endogenous genomic sites in live cells and follow dynamic changes in these marks upon drug treatment, induction of epigenetic enzymes and during the cell cycle. We anticipate that this versatile technology will improve our understanding of how specific epigenetic signatures are set, erased and maintained during embryonic development or disease onset.Tools for imaging epigenetic modifications can shed light on the regulation of epigenetic processes. Here, the authors present a fluorescence complementation approach for detection of DNA and histone methylation at endogenous genomic sites allowing following of dynamic changes of these marks by live-cell microscopy.

Lungu, Pinter, Broche, Rathert, Jeltsch (2017) Modular fluorescence complementation sensors for live cell detection of epigenetic signals at endogenous genomic sites. Nature Communications 8:649

Investigation of the fundamental role of epigenetic processes requires methods for the locus-specific detection of epigenetic modifications in living cells. Here, we address this urgent demand by developing four modular fluorescence complementation-based epigenetic biosensors for live-cell microscopy applications. These tools combine engineered DNA-binding proteins with domains recognizing defined epigenetic marks, both fused to non-fluorescent fragments of a fluorescent protein. The presence of the epigenetic mark at the target DNA sequence leads to the reconstitution of a functional fluorophore. With this approach, we could for the first time directly detect DNA methylation and histone 3 lysine 9 trimethylation at endogenous genomic sites in live cells and follow dynamic changes in these marks upon drug treatment, induction of epigenetic enzymes and during the cell cycle. We anticipate that this versatile technology will improve our understanding of how specific epigenetic signatures are set, erased and maintained during embryonic development or disease onset.Tools for imaging epigenetic modifications can shed light on the regulation of epigenetic processes. Here, the authors present a fluorescence complementation approach for detection of DNA and histone methylation at endogenous genomic sites allowing following of dynamic changes of these marks by live-cell microscopy.

Link

Maier et al. (2017) Design of synthetic epigenetic circuits featuring memory effects and reversible switching based on DNA methylation. Nature Communcations 8, 15336
 
Epigenetic systems store information in DNA methylation patterns in a durable but reversible manner, but have not been regularly used in synthetic biology. Here, we designed synthetic epigenetic memory systems using DNA methylation sensitive engineered zinc finger proteins to repress a memory operon comprising the CcrM methyltransferase and a reporter. Triggering by heat, nutrients, ultraviolet irradiation or DNA damaging compounds induces CcrM expression and DNA methylation. In the induced on-state, methylation in the operator of the memory operon prevents zinc finger protein binding leading to positive feedback and permanent activation. Using an mf-Lon protease degradable CcrM variant enables reversible switching. Epigenetic memory systems have numerous potential applications in synthetic biology, including life biosensors, death switches or induction systems for industrial protein production. The large variety of bacterial DNA methyltransferases potentially allows for massive multiplexing of signal storage and logical operations depending on more than one input signal.
 

Link

Kudithipudi & Jeltsch (2016) Approaches and Guidelines for the Identification of Novel Substrates of Protein Lysine Methyltransferases. Cell Chemical Biology 23, 1049-55

Protein lysine methylation is emerging as a general post-translational modification (PTM) with essential functions regulating protein stability, activity, and protein-protein interactions. One of the outstanding challenges in this field is linking protein lysine methyltransferases (PKMTs) with specific substrates and lysine methylation events in a systematic manner. Inability to validate reported PKMT substrates delayed progress in the field and cast unnecessary doubt about protein lysine methylation as a truly general PTM. Here, we aim to provide a concise guide to help avoid some of the most common pitfalls in studies searching for new PKMT substrates and propose a set of seven basic biochemical rules: (1) include positive controls; (2) use target lysine mutations of substrate proteins as negative controls; (3) use inactive enzyme variants as negative controls; (4) report quantitative methylation data; (5) consider PKMT specificity; (6) validate methyl lysine antibodies; and (7) connect cellular and in vitro results. We explain the logic behind them and discuss how they should be implemented in the experimental work.

 

Link

Jeltsch A, Jurkowska RZ (2016) Allosteric control of mammalian DNA methyltransferases - a new regulatory paradigm. Nucleic Acids Res. 44(18):8556-8575

After almost 40 years of intensive research in the DNA methylation field, we have learned a great deal about the
biochemical, structural and enzymatic properties of the mammalian DNA methyltransferases. However, the regulation
of these fascinating enzymes in cells has only begun to be uncovered. Importantly, it has been lately realized that
the precise control of DNMT activity is critically involved in the generation and maintenance of the dynamic DNA
methylation patterns in living cells. Recent crystallographic studies with DNMT1 and DNMT3A revealed that both enzymes unexpectedly undergo large domain rearrangements, which allosterically regulate their catalytic activity. This unforeseen discovery has led to the important conclusion that by influencing domain rearrangements, any PTMs or interaction partner (be it a protein, an allosteric DNA or a noncoding RNA) at various parts of the methyltransferases
could directly regulate the enzymatic activity and specificity of the DNMTs via allosteric effects, providing new and fascinating perspectives on the investigation of the effects of interactors and PTMs on these enzymes, which are presented and discussed in this review.

Link

Kungulovski & Jeltsch (2016) Epigenome Editing: State of the Art, Concepts, and Perspectives. Trends in Genetics 32, 101-113

Epigenome editing refers to the directed alteration of chromatin marks at specific genomic loci by using targeted EpiEffectors which comprise designed DNA recognition domains (zinc finger, TAL effector, or modified CRISPR/Cas9 complex) and catalytic domains from a chromatin-modifying enzyme. Epigenome editing is a promising approach for durable gene regulation, with many applications in basic research including the investigation of the regulatory functions and logic of chromatin modifications and cellular reprogramming. From a clinical point of view, targeted regulation of disease-related genes offers novel therapeutic avenues for many diseases. We review here the progress made in this field and discuss open questions in epigenetic regulation and its stability, methods to increase the specificity of epigenome editing, and improved delivery methods for targeted EpiEffectors. Future work will reveal if the approach of epigenome editing fulfills its great promise in basic research and clinical applications.

 

Link

Bis 2015

Kungulovski et al. (2014) Application of histone modification-specific interaction domains as an alternative to antibodies. Genome Research 24(11): 1842-53

Post-translational modifications (PTMs) of histones constitute a major chromatin indexing mechanism, and their proper characterization is of highest biological importance. So far, PTM-specific antibodies have been the standard reagent for studying histone PTMs despite caveats such as lot-to-lot variability of specificity and binding affinity. Herein, we successfully employed naturally occurring and engineered histone modification interacting domains for detection and identification of histone PTMs and ChIP-like enrichment of different types of chromatin. Our results demonstrate that histone interacting domains are robust and highly specific reagents that can replace or complement histone modification antibodies. These domains can be produced recombinantly in Escherichia coli at low cost and constant quality. Protein design of reading domains allows for generation of novel specificities, addition of affinity tags, and preparation of PTM binding pocket variants as matching negative controls, which is not possible with antibodies.

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Jeltsch & Jurkowska (2014) New concepts in DNA Methylation. Trends in Biochemical Sciences, 39(7):310-18

The widely-cited model of maintenance of DNA methylation at CpG sites implies that DNA methylation is introduced by the Dnmt3 de novo DNA methyltransferases during early development, and methylation at hemimethylated CpG sites is specifically maintained by the Dnmt1 maintenance methyltransferase. However, substantial experimental evidence from the past decade indicates that this simple model needs to be revised. DNA methylation can be described by a dynamic stochastic model, in which DNA methylation at each site is determined by the local activity of DNA methyltransferases (Dnmts), DNA demethylases, and the DNA replication rate. Through the targeting and regulation of these enzymes, DNA methylation is controlled by the network of chromatin marks.

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Jurkowska & Jeltsch (2013) Genomic Imprinting—The Struggle of the Genders at the Molecular Level. Angewandte Chemie 52, 13524-36

Genomic imprinting, the parent of origin-dependent expression of genes, has been discovered as a fascinating example of the control of gene expression by epigenetic processes in the human body. It affects about 100 genes, which are often involved in growth and development. In this Review, we discuss the mechanisms leading to the generation of gender-specific imprints in form of DNA methylation marks, their preservation during growth and development of the organism, and the processes that translate parental methylation marks into monoallelic gene expression. We discuss the gender-specific dimorphic nature of imprints from an evolutionary point of view and present the prevalent model that molecular imprinting mediates a conflict of interest between the parents that occurs in viviparous animals. Finally, we summarize the relevance of parental imprinting for human health.

Link

Jeltsch (2013) Oxygen, epigenetic signaling and the evolution of early life. Trends in Biochemical Sciences, 38(4):172-6

After approximately 3 billion years of unicellular life on Earth, multicellular animals appeared some 600 million years ago, followed by the rapid emergence of most animal phyla during the Cambrian radiation. This evolutionary jump was paralleled by an increase in atmospheric oxygen, which I propose allowed the generation of epigenetic signaling systems that are essential for cellular differentiation in animals. Epigenetic signaling is based on the reversible deposition of chemically stable marks in DNA and histone proteins, with methylation of cytosine and lysine residues, respectively, playing a central role. Recent evidence indicates that the removal of such methyl groups critically depends on oxygenases. Hence, reversible epigenetic systems could only appear after accumulation of oxygen in the atmosphere.

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Dhayalan et al. (2011) Specificity analysis based identification of new methylation targets of the SET7/9 protein lysine methyltransferase. Chemistry & Biology 18, 111-120

We applied peptide array methylation to determine an optimized target sequence for the SET7/9 (KMT7) protein lysine methyltransferase. Based on this, we identified 91 new peptide substrates from human proteins, many of them better than known substrates. We confirmed methylation of corresponding protein domains in vitro and in vivo with a high success rate for strongly methylated peptides and showed methylation of nine nonhistone proteins (AKA6, CENPC1, MeCP2, MINT, PPARBP, ZDH8, Cullin1, IRF1, and [weakly] TTK) and of H2A and H2B, which more than doubles the number of known SET7/9 targets. SET7/9 is inhibited by phosphorylation of histone and nonhistone substrate proteins. One lysine in the MINT protein is dimethylated in vitro and in vivo demonstrating that the product pattern created by SET7/9 depends on the amino acid sequence context of the target site.

 

Link zum Artikel

Bock et al. (2011) Detailed specificity analysis of antibodies binding to modified histone tails with peptide arrays. Epigenetics 6, 265-263

Chromatin structure is greatly influenced by histone tail post-translational modifications (PTM), which also play a central role in epigenetic processes. Antibodies against modified histone tails are central research reagents in chromatin biology and molecular epigenetics. We applied Celluspots peptide arrays for the specificity analysis of 36 commercial antibodies from different suppliers which are directed towards modified histone tails. The arrays contained 384 peptides from 8 different regions of the N-terminal tails of histones, viz. H3 1-19, 7-26, 16-35 and 26-45, H4 1-19 and 11-30, H2A 1-19 and H2B 1-19, featuring 59 post-translational modifications in many different combinations. Using various controls we document the reliability of the method. Our analysis revealed previously undocumented details in the specificity profile. Most of the antibodies bound well to the PTM they have been raised for, but some failed. In addition some antibodies showed high cross-reactivity and most antibodies were inhibited by specific additional PTMs close to the primary one. Furthermore, specificity profiles for antibodies directed towards the same modification sometimes were very different. The specificity of antibodies used in epigenetic research is an important issue. We provide a catalog of antibody specificity profiles for 36 widely used commercial histone tail PTM antibodies. Better knowledge about the specificity profiles of antibodies will enable researchers to implement necessary control experiments in biological studies and allow more reliable interpretation of biological experiments using these antibodies.

Link zum Artikel

Jeltsch (2010) Phylogeny of Methylomes, Science 328, 837-8

The DNA of most species is methylated, containing the modified base 5-methylcytosine. This modification has a role in silencing gene expression, among other important functions. Advances in sequencing methods have allowed measurement of the first complete genome-wide DNA methylation map (“methylome”) of the model plant Arabidopsis thaliana and human cells. Studies by Feng et al. and by Zemach et al. on page 916 of this issue now expand this list by providing genome-wide methylomes for 20 additional species, revealing important conserved features and phylogenetic relationships of the methylation machinery.

Link zum Artikel

Rathert et al. (2008) Protein lysine methyltransferase G9a acts on non-histone targets. Nat. Chem. Biol. 4, 344-6

By methylation of peptide arrays, we determined the specificity profile of the protein methyltransferase G9a. We show that it mostly recognizes an Arg-Lys sequence and that its activity is inhibited by methylation of the arginine residue. Using the specificity profile, we identified new non-histone protein targets of G9a, including CDYL1, WIZ, ACINUS and G9a (automethylation), as well as peptides derived from CSB. We demonstrate potential downstream signaling pathways for methylation of non-histone proteins.

 

Link zum Artikel

Rathert et al. (2008) Analysis of the Substrate Specificity of the Dim-5 Histone Lysine Methyltransferases Using Peptide Arrays. Chemistry & Biology 15, 5-11

Histone methylation is an epigenetic mark essential for gene regulation and development. We introduce peptide SPOT synthesis to study sequence specificity of the Dim-5 histone-3 lysine-9 methyltransferase. Dim-5 recognizes R8-G12 of the H3 tail with T11 and G12 being the most important specificity determinants. Exchange of H3 tail residue S10 and T11 by E strongly reduced methylation by Dim-5, suggesting that phosphorylation of S10 or T11 may regulate the activity of Dim-5. In the Dim-5/peptide structure, E227 interacts with H3R8 and D209 with H3-S10. Mutations of E227 or D209 caused predictable changes in the substrate preference, illustrating that peptide recognition of histone methyltransferases can be altered by protein design. Comparative analyses of peptide arrays with wild-type and mutant enzymes, therefore, are well suited to investigate the target specificity of protein methyltransferases and study epigenetic crosstalk.

 

Link zum Artikel

Jia et al. (2007) Structure of the Dnmt3L-Dnmt3a Complex Suggests a Model for de novo DNA Methylation. Nature 449, 248-51

Genetic imprinting, found in flowering plants and placental mammals, uses DNA methylation to yield gene expression that is dependent on the parent of origin. DNA methyltransferase 3a (Dnmt3a) and its regulatory factor, DNA methyltransferase 3-like protein (Dnmt3L), are both required for the de novo DNA methylation of imprinted genes in mammalian germ cells. Dnmt3L interacts specifically with unmethylated lysine 4 of histone H3 through its amino-terminal PHD (plant homeodomain)-like domain. Here we show, with the use of crystallography, that the carboxy-terminal domain of human Dnmt3L interacts with the catalytic domain of Dnmt3a, demonstrating that Dnmt3L has dual functions of binding the unmethylated histone tail and activating DNA methyltransferase. The complexed C-terminal domains of Dnmt3a and Dnmt3L showed further dimerization through Dnmt3a-Dnmt3a interaction, forming a tetrameric complex with two active sites. Substitution of key non-catalytic residues at the Dnmt3a-Dnmt3L interface or the Dnmt3a-Dnmt3a interface eliminated enzymatic activity. Molecular modelling of a DNA-Dnmt3a dimer indicated that the two active sites are separated by about one DNA helical turn. The C-terminal domain of Dnmt3a oligomerizes on DNA to form a nucleoprotein filament. A periodicity in the activity of Dnmt3a on long DNA revealed a correlation of methylated CpG sites at distances of eight to ten base pairs, indicating that oligomerization leads Dnmt3a to methylate DNA in a periodic pattern. A similar periodicity is observed for the frequency of CpG sites in the differentially methylated regions of 12 maternally imprinted mouse genes. These results suggest a basis for the recognition and methylation of differentially methylated regions in imprinted genes, involving the detection of both nucleosome modification and CpG spacing.

 

Link zum Artikel

Horton et al. (2005) Transition from non-specific to specific DNA interaction along the DNA recognition pathway of DAM methyltransferase. Cell 121, 349-61

DNA methyltransferases methylate target bases within specific nucleotide sequences. Three structures are described for bacteriophage T4 DNA-adenine methyltransferase (T4Dam) in ternary complexes with partially and fully specific DNA and a methyl-donor analog. We also report the effects of substitutions in the related Escherichia coli DNA methyltransferase (EcoDam), altering residues corresponding to those involved in specific interaction with the canonical GATC target sequence in T4Dam. We have identified two types of protein-DNA interactions: discriminatory contacts, which stabilize the transition state and accelerate methylation of the cognate site, and antidiscriminatory contacts, which do not significantly affect methylation of the cognate site but disfavor activity at noncognate sites. These structures illustrate the transition in enzyme-DNA interaction from nonspecific to specific interaction, suggesting that there is a temporal order for formation of specific contacts.

 

Link zum Artikel

Vollständige Publikationsliste von Prof. Jeltsch

  1. 2021

    1. 264. J. Broche, G. Kungulovski, P. Bashtrykov, P. Rathert, and A. Jeltsch, “Genome-wide investigation of the dynamic changes of epigenome modifications after global DNA methylation editing,” Nucleic Acids Res, vol. 49, no. 1, Art. no. 1, 2021, doi: 10.1093/nar/gkaa1169.
  2. 2020

    1. 263. S. Adam et al., “DNA sequence-dependent activity and base flipping mechanisms of DNMT1 regulate genome-wide DNA methylation,” Nat Commun, vol. 11, no. 1, Art. no. 1, 2020, doi: 10.1038/s41467-020-17531-8.
    2. 262. C. Dong et al., “Recognition of nonproline N-terminal residues by the Pro/N-degron pathway,” Proc Natl Acad Sci U S A, vol. 117, no. 25, Art. no. 25, 2020, doi: 10.1073/pnas.2007085117.
    3. 261. M. Dukatz, S. Adam, M. Biswal, J. Song, P. Bashtrykov, and A. Jeltsch, “Complex DNA sequence readout mechanisms of the DNMT3B DNA methyltransferase,” Nucleic Acids Res, vol. 48, no. 20, Art. no. 20, 2020, doi: 10.1093/nar/gkaa938.
    4. 260. L. Gao et al., “Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms,” Nat Commun, vol. 11, no. 1, Art. no. 1, 2020, doi: 10.1038/s41467-020-17109-4.
    5. 259. D. Hofacker, J. Broche, L. Laistner, S. Adam, P. Bashtrykov, and A. Jeltsch, “Engineering of Effector Domains for Targeted DNA Methylation with Reduced Off-Target Effects,” Int J Mol Sci, vol. 21, no. 2, Art. no. 2, 2020, doi: 10.3390/ijms21020502.
    6. 258. M. S. Khella, A. Brohm, S. Weirich, and A. Jeltsch, “Mechanistic Insights into the Allosteric Regulation of the Clr4 Protein Lysine Methyltransferase by Autoinhibition and Automethylation,” Int J Mol Sci, vol. 21, no. 22, Art. no. 22, 2020, doi: 10.3390/ijms21228832.
    7. 257. P. Lutsik et al., “Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone,” Nat Commun, vol. 11, no. 1, Art. no. 1, 2020, doi: 10.1038/s41467-020-18955-y.
    8. 256. M. K. Schuhmacher et al., “Sequence specificity analysis of the SETD2 protein lysine methyltransferase and discovery of a SETD2 super-substrate,” Commun Biol, vol. 3, no. 1, Art. no. 1, 2020, doi: 10.1038/s42003-020-01223-6.
    9. 255. D. Stohr, A. Jeltsch, and M. Rehm, “TRAIL receptor signaling: From the basics of canonical signal transduction toward its entanglement with ER stress and the unfolded protein response,” Int Rev Cell Mol Biol, vol. 351, pp. 57–99, 2020, doi: 10.1016/bs.ircmb.2020.02.002.
    10. 254. T. Ullrich, S. Weirich, and A. Jeltsch, “Development of an epigenetic tetracycline sensor system based on DNA methylation,” PLoS One, vol. 15, no. 5, Art. no. 5, 2020, doi: 10.1371/journal.pone.0232701.
    11. 253. S. Weirich, M. K. Schuhmacher, S. Kudithipudi, C. Lungu, A. D. Ferguson, and A. Jeltsch, “Analysis of the Substrate Specificity of the SMYD2 Protein Lysine Methyltransferase and Discovery of Novel Non-Histone Substrates,” Chembiochem, vol. 21, no. 1–2, Art. no. 1–2, 2020, doi: 10.1002/cbic.201900582.
  3. 2019

    1. 252. A. Brohm et al., “Somatic Cancer Mutations in the SUV420H1 Protein Lysine Methyltransferase Modulate Its Catalytic Activity,” J Mol Biol, vol. 431, no. 17, Art. no. 17, 2019, doi: 10.1016/j.jmb.2019.06.021.
    2. 251. M. Dukatz, C. E. Requena, M. Emperle, P. Hajkova, P. Sarkies, and A. Jeltsch, “Mechanistic Insights into Cytosine-N3 Methylation by DNA Methyltransferase DNMT3A,” J Mol Biol, vol. 431, no. 17, Art. no. 17, 2019, doi: 10.1016/j.jmb.2019.06.015.
    3. 250. M. Dukatz et al., “H3K36me2/3 Binding and DNA Binding of the DNA Methyltransferase DNMT3A PWWP Domain Both Contribute to its Chromatin Interaction,” J Mol Biol, vol. 431, no. 24, Art. no. 24, 2019, doi: 10.1016/j.jmb.2019.09.006.
    4. 249. M. Emperle et al., “Mutations of R882 change flanking sequence preferences of the DNA methyltransferase DNMT3A and cellular methylation patterns,” Nucleic Acids Res, vol. 47, no. 21, Art. no. 21, 2019, doi: 10.1093/nar/gkz911.
    5. 248. A. Jeltsch, J. Broche, and P. Bashtrykov, “Molecular Processes Connecting DNA Methylation Patterns with DNA Methyltransferases and Histone Modifications in Mammalian Genomes,” Genes (Basel), vol. 10, no. 5, Art. no. 5, 2019, doi: 10.3390/genes10050388.
    6. 247. A. Jeltsch, “Novel Insights into Peptide Binding and Conformational Dynamics of UHRF1,” Structure, vol. 27, no. 3, Art. no. 3, 2019, doi: 10.1016/j.str.2019.02.003.
    7. 246. A. Jeltsch, J. Broche, C. Lungu, and P. Bashtrykov, “Biotechnological Applications of MBD Domain Proteins for DNA Methylation Analysis,” J Mol Biol, 2019, doi: 10.1016/j.jmb.2019.08.020.
    8. 245. A. Jeltsch and H. Gowher, “Editorial-Role of DNA Methyltransferases in the Epigenome,” Genes (Basel), vol. 10, no. 8, Art. no. 8, 2019, doi: 10.3390/genes10080574.
    9. 244. Z. Li et al., “Cyclin D1 integrates G9a-mediated histone methylation,” Oncogene, vol. 38, no. 22, Art. no. 22, 2019, doi: 10.1038/s41388-019-0723-8.
    10. 243. R. Mauser and A. Jeltsch, “Application of modified histone peptide arrays in chromatin research,” Arch Biochem Biophys, vol. 661, pp. 31–38, 2019, doi: 10.1016/j.abb.2018.10.019.
  4. 2018

    1. 242. P. Bashtrykov and A. Jeltsch, “Allele-Specific Epigenome Editing,” Methods Mol Biol, vol. 1767, pp. 137–146, 2018, doi: 10.1007/978-1-4939-7774-1_6.
    2. 241. P. Bashtrykov and A. Jeltsch, “DNA Methylation Analysis by Bisulfite Conversion Coupled to Double Multiplexed Amplicon-Based Next-Generation Sequencing (NGS),” Methods Mol Biol, vol. 1767, pp. 367–382, 2018, doi: 10.1007/978-1-4939-7774-1_20.
    3. 240. M. Emperle et al., “The DNMT3A R882H mutant displays altered flanking sequence preferences,” Nucleic Acids Res, vol. 46, no. 6, Art. no. 6, 2018, doi: 10.1093/nar/gky168.
    4. 239. M. Emperle et al., “The DNMT3A R882H mutation does not cause dominant negative effects in purified mixed DNMT3A/R882H complexes,” Sci Rep, vol. 8, no. 1, Art. no. 1, 2018, doi: 10.1038/s41598-018-31635-8.
    5. 238. H. Gowher and A. Jeltsch, “Mammalian DNA methyltransferases: new discoveries and open questions,” Biochem Soc Trans, vol. 46, no. 5, Art. no. 5, 2018, doi: 10.1042/BST20170574.
    6. 237. L. Halby et al., “Hijacking DNA methyltransferase transition state analogues to produce chemical scaffolds for PRMT inhibitors,” Philos Trans R Soc Lond B Biol Sci, vol. 373, no. 1748, Art. no. 1748, 2018, doi: 10.1098/rstb.2017.0072.
    7. 236. M. L. Hohenstatt et al., “PWWP-DOMAIN INTERACTOR OF POLYCOMBS1 Interacts with Polycomb-Group Proteins and Histones and Regulates Arabidopsis Flowering and Development,” Plant Cell, vol. 30, no. 1, Art. no. 1, 2018, doi: 10.1105/tpc.17.00117.
    8. 235. M. E. Jakobsson et al., “The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates,” Nat Commun, vol. 9, no. 1, Art. no. 1, 2018, doi: 10.1038/s41467-018-05646-y.
    9. 234. A. Jeltsch, “From Bioengineering to CRISPR/Cas9 - A Personal Retrospective of 20 Years of Research in Programmable Genome Targeting,” Front Genet, vol. 9, p. 5, 2018, doi: 10.3389/fgene.2018.00005.
    10. 233. A. Jeltsch, J. Broche, and P. Bashtrykov, “Molecular Processes Connecting DNA Methylation Patterns with DNA Methyltransferases and Histone Modifications in Mammalian Genomes,” Genes (Basel), vol. 9, no. 11, Art. no. 11, 2018, doi: 10.3390/genes9110566.
    11. 232. J. A. H. Maier and A. Jeltsch, “Design and Application of 6mA-Specific Zinc-Finger Proteins for the Readout of DNA Methylation,” Methods Mol Biol, vol. 1867, pp. 29–41, 2018, doi: 10.1007/978-1-4939-8799-3_3.
    12. 231. R. Mauser, G. Kungulovski, D. Meral, D. Maisch, and A. Jeltsch, “Application of mixed peptide arrays to study combinatorial readout of chromatin modifications,” Biochimie, vol. 146, pp. 14–19, 2018, doi: 10.1016/j.biochi.2017.11.008.
    13. 230. A. Rajavelu et al., “Chromatin-dependent allosteric regulation of DNMT3A activity by MeCP2,” Nucleic Acids Res, vol. 46, no. 17, Art. no. 17, 2018, doi: 10.1093/nar/gky715.
    14. 229. A. A. Rawluszko-Wieczorek, F. Knodel, R. Tamas, A. Dhayalan, and A. Jeltsch, “Identification of protein lysine methylation readers with a yeast three-hybrid approach,” Epigenetics Chromatin, vol. 11, no. 1, Art. no. 1, 2018, doi: 10.1186/s13072-018-0175-3.
    15. 228. S. Rosic et al., “Evolutionary analysis indicates that DNA alkylation damage is a byproduct of cytosine DNA methyltransferase activity,” Nat Genet, vol. 50, no. 3, Art. no. 3, 2018, doi: 10.1038/s41588-018-0061-8.
    16. 227. M. G. Rots and A. Jeltsch, “Editing the Epigenome: Overview, Open Questions, and Directions of Future Development,” Methods Mol Biol, vol. 1767, pp. 3–18, 2018, doi: 10.1007/978-1-4939-7774-1_1.
    17. 226. M. K. Schuhmacher et al., “The Legionella pneumophila Methyltransferase RomA Methylates Also Non-histone Proteins during Infection,” J Mol Biol, vol. 430, no. 13, Art. no. 13, 2018, doi: 10.1016/j.jmb.2018.04.032.
  5. 2017

    1. 225. P. Bashtrykov and A. Jeltsch, “Epigenome Editing in the Brain,” Adv Exp Med Biol, vol. 978, pp. 409–424, 2017, doi: 10.1007/978-3-319-53889-1_21.
    2. 224. O. Engmann et al., “Cocaine-Induced Chromatin Modifications Associate With Increased Expression and Three-Dimensional Looping of Auts2,” Biol Psychiatry, vol. 82, no. 11, Art. no. 11, 2017, doi: 10.1016/j.biopsych.2017.04.013.
    3. 223. L. Ferry et al., “Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation,” Mol Cell, vol. 67, no. 4, Art. no. 4, 2017, doi: 10.1016/j.molcel.2017.07.012.
    4. 222. M. Hassanzadeh et al., “Discovery of Novel and Selective DNA Methyltransferase 1 Inhibitors by Pharmacophore and Docking-Based Virtual Screening,” Chemistryselect, vol. 2, no. 27, Art. no. 27, 2017, doi: 10.1002/slct.201701734.
    5. 221. L. Imre et al., “Nucleosome stability measured in situ by automated quantitative imaging,” Sci Rep, vol. 7, no. 1, Art. no. 1, 2017, doi: 10.1038/s41598-017-12608-9.
    6. 220. A. Jeltsch et al., “Mechanism and biological role of Dnmt2 in Nucleic Acid Methylation,” RNA Biol, vol. 14, no. 9, Art. no. 9, 2017, doi: 10.1080/15476286.2016.1191737.
    7. 219. R. Z. Jurkowska et al., “H3K14ac is linked to methylation of H3K9 by the triple Tudor domain of SETDB1,” Nat Commun, vol. 8, no. 1, Art. no. 1, 2017, doi: 10.1038/s41467-017-02259-9.
    8. 218. S. Kaiser, T. P. Jurkowski, S. Kellner, D. Schneider, A. Jeltsch, and M. Helm, “The RNA methyltransferase Dnmt2 methylates DNA in the structural context of a tRNA,” RNA Biol, vol. 14, no. 9, Art. no. 9, 2017, doi: 10.1080/15476286.2016.1236170.
    9. 217. S. Kudithipudi, M. K. Schuhmacher, A. F. Kebede, and A. Jeltsch, “The SUV39H1 Protein Lysine Methyltransferase Methylates Chromatin Proteins Involved in Heterochromatin Formation and VDJ Recombination,” ACS Chem Biol, vol. 12, no. 4, Art. no. 4, 2017, doi: 10.1021/acschembio.6b01076.
    10. 216. D. Kusevic, S. Kudithipudi, N. Iglesias, D. Moazed, and A. Jeltsch, “Clr4 specificity and catalytic activity beyond H3K9 methylation,” Biochimie, vol. 135, pp. 83–88, 2017, doi: 10.1016/j.biochi.2017.01.013.
    11. 215. C. Lungu, S. Pinter, J. Broche, P. Rathert, and A. Jeltsch, “Modular fluorescence complementation sensors for live cell detection of epigenetic signals at endogenous genomic sites,” Nat Commun, vol. 8, no. 1, Art. no. 1, 2017, doi: 10.1038/s41467-017-00457-z.
    12. 214. J. A. H. Maier, R. Mohrle, and A. Jeltsch, “Design of synthetic epigenetic circuits featuring memory effects and reversible switching based on DNA methylation,” Nat Commun, vol. 8, p. 15336, 2017, doi: 10.1038/ncomms15336.
    13. 213. R. Mauser, G. Kungulovski, C. Keup, R. Reinhardt, and A. Jeltsch, “Application of dual reading domains as novel reagents in chromatin biology reveals a new H3K9me3 and H3K36me2/3 bivalent chromatin state,” Epigenetics Chromatin, vol. 10, no. 1, Art. no. 1, 2017, doi: 10.1186/s13072-017-0153-1.
    14. 212. R. Mauser, G. Kungulovski, D. Meral, D. Maisch, and A. Jeltsch, “Application of mixed peptide arrays to study combinatorial readout of chromatin modifications,” Biochimie, 2017, doi: 10.1016/j.biochi.2017.11.008.
    15. 211. M. Schuhmacher, D. Kusevic, S. Kudithipudi, and A. Jeltsch, “Kinetic Analysis of the Inhibition of the NSD1, NSD2 and SETD2 Protein Lysine Methyltransferases by a K36M Oncohistone Peptide,” Chemistryselect, vol. 2, no. 29, Art. no. 29, 2017, doi: 10.1002/slct.201701940.
    16. 210. P. Stepper et al., “Efficient targeted DNA methylation with chimeric dCas9-Dnmt3a-Dnmt3L methyltransferase,” Nucleic Acids Res, vol. 45, no. 4, Art. no. 4, 2017, doi: 10.1093/nar/gkw1112.
    17. 209. S. Weirich, S. Kudithipudi, and A. Jeltsch, “Somatic cancer mutations in the MLL1 histone methyltransferase modulate its enzymatic activity and dependence on the WDR5/RBBP5/ASH2L complex,” Mol Oncol, vol. 11, no. 4, Art. no. 4, 2017, doi: 10.1002/1878-0261.12041.
  6. 2016

    1. 208. P. Bashtrykov, G. Kungulovski, and A. Jeltsch, “Correction of aberrant imprinting by allele-specific epigenome editing,” Clin Pharmacol Ther, vol. 99, no. 5, Art. no. 5, 2016, doi: 10.1002/cpt.295.
    2. 207. H. Hoenicka et al., “Level of tissue differentiation influences the activation of a heat-inducible flower-specific system for genetic containment in poplar (Populus tremula L.),” Plant Cell Rep, vol. 35, no. 2, Art. no. 2, 2016, doi: 10.1007/s00299-015-1890-x.
    3. 206. A. Jeltsch et al., “Mechanism and biological role of Dnmt2 in Nucleic Acid Methylation,” RNA Biol, pp. 1–16, 2016, doi: 10.1080/15476286.2016.1191737.
    4. 205. A. Jeltsch and R. Z. Jurkowska, “Allosteric control of mammalian DNA methyltransferases - a new regulatory paradigm,” Nucleic Acids Res, vol. 44, no. 18, Art. no. 18, 2016, doi: 10.1093/nar/gkw723.
    5. 204. R. Z. Jurkowska and A. Jeltsch, “DNA Methyltransferases - Role and Function Preface,” DNA Methyltransferases - Role and Function, vol. 945, pp. V–Vi, 2016, doi: Book_Doi 10.1007/978-3-319-43624-1.
    6. 203. R. Z. Jurkowska and A. Jeltsch, “Enzymology of Mammalian DNA Methyltransferases,” Adv Exp Med Biol, vol. 945, pp. 87–122, 2016, doi: 10.1007/978-3-319-43624-1_5.
    7. 202. R. Z. Jurkowska and A. Jeltsch, “Mechanisms and Biological Roles of DNA Methyltransferases and DNA Methylation: From Past Achievements to Future Challenges,” Adv Exp Med Biol, vol. 945, pp. 1–17, 2016, doi: 10.1007/978-3-319-43624-1_1.
    8. 201. S. Kaiser, T. P. Jurkowski, S. Kellner, D. Schneider, A. Jeltsch, and M. Helm, “The RNA methyltransferase Dnmt2 methylates DNA in the structural context of a tRNA,” RNA Biol, pp. 1–11, 2016, doi: 10.1080/15476286.2016.1236170.
    9. 200. S. Kudithipudi and A. Jeltsch, “Approaches and Guidelines for the Identification of Novel Substrates of Protein Lysine Methyltransferases,” Cell Chem Biol, vol. 23, no. 9, Art. no. 9, 2016, doi: 10.1016/j.chembiol.2016.07.013.
    10. 199. G. Kungulovski, R. Mauser, R. Reinhardt, and A. Jeltsch, “Application of recombinant TAF3 PHD domain instead of anti-H3K4me3 antibody,” Epigenetics Chromatin, vol. 9, p. 11, 2016, doi: 10.1186/s13072-016-0061-9.
    11. 198. G. Kungulovski and A. Jeltsch, “Epigenome Editing: State of the Art, Concepts, and Perspectives,” Trends Genet, vol. 32, no. 2, Art. no. 2, 2016, doi: 10.1016/j.tig.2015.12.001.
    12. 197. D. Kusevic, S. Kudithipudi, and A. Jeltsch, “Substrate Specificity of the HEMK2 Protein Glutamine Methyltransferase and Identification of Novel Substrates,” J Biol Chem, vol. 291, no. 12, Art. no. 12, 2016, doi: 10.1074/jbc.M115.711952.
    13. 196. O. V. Lukashevich, N. A. Cherepanova, R. Z. Jurkovska, A. Jeltsch, and E. S. Gromova, “Conserved motif VIII of murine DNA methyltransferase Dnmt3a is essential for methylation activity,” BMC Biochem, vol. 17, p. 7, 2016, doi: 10.1186/s12858-016-0064-y.
    14. 195. M. K. Schuhmacher, S. Kudithipudi, and A. Jeltsch, “Investigation of H2AX methylation by the SUV39H2 protein lysine methyltransferase,” FEBS Lett, vol. 590, no. 12, Art. no. 12, 2016, doi: 10.1002/1873-3468.12216.
    15. 194. S. Weirich, S. Kudithipudi, and A. Jeltsch, “Specificity of the SUV4-20H1 and SUV4-20H2 protein lysine methyltransferases and methylation of novel substrates,” J Mol Biol, vol. 428, no. 11, Art. no. 11, 2016, doi: 10.1016/j.jmb.2016.04.015.
  7. 2015

    1. 193. P. Bashtrykov and A. Jeltsch, “DNMT1-associated DNA methylation changes in cancer,” Cell Cycle, vol. 14, no. 1, Art. no. 1, 2015, doi: 10.4161/15384101.2014.989963.
    2. 192. W. Elhardt, R. Shanmugam, T. P. Jurkowski, and A. Jeltsch, “Somatic cancer mutations in the DNMT2 tRNA methyltransferase alter its catalytic properties,” Biochimie, vol. 112, pp. 66–72, 2015, doi: 10.1016/j.biochi.2015.02.022.
    3. 191. A. Jeltsch, W. Wende, P. Friedhoff, and B. L. Stoddard, “Editorial: Alfred Pingoud (1945-2015),” Nucleic Acids Res, vol. 43, no. 16, Art. no. 16, 2015, doi: 10.1093/nar/gkv846.
    4. 190. R. Jurkowska, M. Emperle, A. Rajavelu, W. Nellen, and A. Jeltsch, “Controlling the methylation writer: regulation of Dnmt3a DNA methyltransferase by oligomerisation,” Febs Journal, vol. 282, pp. 69–69, 2015, [Online]. Available: /brokenurl#<Go to ISI>://000362570601046.
    5. 189. G. Kungulovski, S. Nunna, M. Thomas, U. M. Zanger, R. Reinhardt, and A. Jeltsch, “Targeted epigenome editing of an endogenous locus with chromatin modifiers is not stably maintained,” Epigenetics Chromatin, vol. 8, p. 12, 2015, doi: 10.1186/s13072-015-0002-z.
    6. 188. G. Kungulovski, I. Kycia, R. Mauser, and A. Jeltsch, “Specificity Analysis of Histone Modification-Specific Antibodies or Reading Domains on Histone Peptide Arrays,” Methods Mol Biol, vol. 1348, pp. 275–84, 2015, doi: 10.1007/978-1-4939-2999-3_24.
    7. 187. G. Kungulovski and A. Jeltsch, “Quality of histone modification antibodies undermines chromatin biology research,” F1000Res, vol. 4, p. 1160, 2015, doi: 10.12688/f1000research.7265.2.
    8. 186. G. Kungulovski, R. Mauser, and A. Jeltsch, “Affinity reagents for studying histone modifications & guidelines for their quality control,” Epigenomics, vol. 7, no. 7, Art. no. 7, 2015, doi: 10.2217/epi.15.59.
    9. 185. C. Lungu, K. Muegge, A. Jeltsch, and R. Z. Jurkowska, “An ATPase-deficient variant of the SNF2 family member HELLS shows altered dynamics at pericentromeric heterochromatin,” J Mol Biol, vol. 427, no. 10, Art. no. 10, 2015, doi: 10.1016/j.jmb.2015.03.014.
    10. 184. J. A. Maier, R. F. Albu, T. P. Jurkowski, and A. Jeltsch, “Investigation of the C-terminal domain of the bacterial DNA-(adenine N6)-methyltransferase CcrM,” Biochimie, vol. 119, pp. 60–7, 2015, doi: 10.1016/j.biochi.2015.10.011.
    11. 183. J. A. Maier, S. Ragozin, and A. Jeltsch, “Identification, cloning and heterologous expression of active NiFe-hydrogenase 2 from Citrobacter sp. SG in Escherichia coli,” J Biotechnol, vol. 199, pp. 1–8, 2015, doi: 10.1016/j.jbiotec.2015.01.025.
    12. 182. M. K. Schuhmacher, S. Kudithipudi, D. Kusevic, S. Weirich, and A. Jeltsch, “Activity and specificity of the human SUV39H2 protein lysine methyltransferase,” Biochim Biophys Acta, vol. 1849, no. 1, Art. no. 1, 2015, doi: 10.1016/j.bbagrm.2014.11.005.
    13. 181. R. Shanmugam, J. Fierer, S. Kaiser, M. Helm, T. P. Jurkowski, and A. Jeltsch, “Cytosine methylation of tRNA-Asp by DNMT2 has a role in translation of proteins containing poly-Asp sequences,” Cell Discov, vol. 1, p. 15010, 2015, doi: 10.1038/celldisc.2015.10.
    14. 180. C. Voelcker-Rehage, A. Jeltsch, B. Godde, S. Becker, and U. M. Staudinger, “COMT gene polymorphisms, cognitive performance, and physical fitness in older adults,” Psychology of Sport and Exercise, vol. 20, pp. 20–28, 2015, doi: 10.1016/j.psychsport.2015.04.001.
    15. 179. S. Weirich, D. Kusevic, S. Kudithipudi, and A. Jeltsch, “Investigation of the methylation of Numb by the SET8 protein lysine methyltransferase,” Sci Rep, vol. 5, p. 13813, 2015, doi: 10.1038/srep13813.
    16. 178. S. Weirich, S. Kudithipudi, I. Kycia, and A. Jeltsch, “Somatic cancer mutations in the MLL3-SET domain alter the catalytic properties of the enzyme,” Clin Epigenetics, vol. 7, p. 36, 2015, doi: 10.1186/s13148-015-0075-3.
  8. 2014

    1. 177. S. Asgatay et al., “Synthesis and evaluation of analogues of N-phthaloyl-l-tryptophan (RG108) as inhibitors of DNA methyltransferase 1,” J Med Chem, vol. 57, no. 2, Art. no. 2, 2014, doi: 10.1021/jm401419p.
    2. 176. P. Bashtrykov, G. Jankevicius, R. Z. Jurkowska, S. Ragozin, and A. Jeltsch, “The UHRF1 protein stimulates the activity and specificity of the maintenance DNA methyltransferase DNMT1 by an allosteric mechanism,” J Biol Chem, vol. 289, no. 7, Art. no. 7, 2014, doi: 10.1074/jbc.M113.528893.
    3. 175. P. Bashtrykov, A. Rajavelu, B. Hackner, S. Ragozin, T. Carell, and A. Jeltsch, “Targeted mutagenesis results in an activation of DNA methyltransferase 1 and confirms an autoinhibitory role of its RFTS domain,” Chembiochem, vol. 15, no. 5, Art. no. 5, 2014, doi: 10.1002/cbic.201300740.
    4. 174. R. Deplus et al., “Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a,” Cell Rep, vol. 8, no. 3, Art. no. 3, 2014, doi: 10.1016/j.celrep.2014.06.048.
    5. 173. M. Emperle, A. Rajavelu, R. Reinhardt, R. Z. Jurkowska, and A. Jeltsch, “Cooperative DNA binding and protein/DNA fiber formation increases the activity of the Dnmt3a DNA methyltransferase,” J Biol Chem, vol. 289, no. 43, Art. no. 43, 2014, doi: 10.1074/jbc.M114.572032.
    6. 172. K. Guitot et al., “Label-free measurement of histone lysine methyltransferases activity by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry,” Anal Biochem, vol. 456, pp. 25–31, 2014, doi: 10.1016/j.ab.2014.04.006.
    7. 171. A. Jeltsch and R. Z. Jurkowska, “New concepts in DNA methylation,” Trends Biochem Sci, vol. 39, no. 7, Art. no. 7, 2014, doi: 10.1016/j.tibs.2014.05.002.
    8. 170. S. Kudithipudi, C. Lungu, P. Rathert, N. Happel, and A. Jeltsch, “Substrate specificity analysis and novel substrates of the protein lysine methyltransferase NSD1,” Chem Biol, vol. 21, no. 2, Art. no. 2, 2014, doi: 10.1016/j.chembiol.2013.10.016.
    9. 169. S. Kudithipudi, D. Kusevic, S. Weirich, and A. Jeltsch, “Specificity analysis of protein lysine methyltransferases using SPOT peptide arrays,” J Vis Exp, no. 93, Art. no. 93, 2014, doi: 10.3791/52203.
    10. 168. S. Kudithipudi and A. Jeltsch, “Role of somatic cancer mutations in human protein lysine methyltransferases,” Biochim Biophys Acta, vol. 1846, no. 2, Art. no. 2, 2014, doi: 10.1016/j.bbcan.2014.08.002.
    11. 167. S. Kudithipudi, D. Kusevic, and A. Jeltsch, “Non-radioactive protein lysine methyltransferase microplate assay based on reading domains,” ChemMedChem, vol. 9, no. 3, Art. no. 3, 2014, doi: 10.1002/cmdc.201300111.
    12. 166. G. Kungulovski et al., “Application of histone modification-specific interaction domains as an alternative to antibodies,” Genome Res, vol. 24, no. 11, Art. no. 11, 2014, doi: 10.1101/gr.170985.113.
    13. 165. I. Kycia, S. Kudithipudi, R. Tamas, G. Kungulovski, A. Dhayalan, and A. Jeltsch, “The Tudor domain of the PHD finger protein 1 is a dual reader of lysine trimethylation at lysine 36 of histone H3 and lysine 27 of histone variant H3t,” J Mol Biol, vol. 426, no. 8, Art. no. 8, 2014, doi: 10.1016/j.jmb.2013.08.009.
    14. 164. S. Nunna, R. Reinhardt, S. Ragozin, and A. Jeltsch, “Targeted methylation of the epithelial cell adhesion molecule (EpCAM) promoter to silence its expression in ovarian cancer cells,” PLoS One, vol. 9, no. 1, Art. no. 1, 2014, doi: 10.1371/journal.pone.0087703.
    15. 163. E. Rilova et al., “Design, synthesis and biological evaluation of 4-amino-N- (4-aminophenyl)benzamide analogues of quinoline-based SGI-1027 as inhibitors of DNA methylation,” ChemMedChem, vol. 9, no. 3, Art. no. 3, 2014, doi: 10.1002/cmdc.201300420.
    16. 162. R. Shanmugam et al., “The Dnmt2 RNA methyltransferase homolog of Geobacter sulfurreducens specifically methylates tRNA-Glu,” Nucleic Acids Res, vol. 42, no. 10, Art. no. 10, 2014, doi: 10.1093/nar/gku256.
  9. 2013

    1. 161. A. Ceccaldi et al., “Identification of novel inhibitors of DNA methylation by screening of a chemical library,” ACS Chem Biol, vol. 8, no. 3, Art. no. 3, 2013, doi: 10.1021/cb300565z.
    2. 160. A. Jeltsch and R. Z. Jurkowska, “Multimerization of the dnmt3a DNA methyltransferase and its functional implications,” Prog Mol Biol Transl Sci, vol. 117, pp. 445–64, 2013, doi: 10.1016/B978-0-12-386931-9.00016-7.
    3. 159. A. Jeltsch, “Oxygen, epigenetic signaling, and the evolution of early life,” Trends Biochem Sci, vol. 38, no. 4, Art. no. 4, 2013, doi: 10.1016/j.tibs.2013.02.001.
    4. 158. R. Z. Jurkowska and A. Jeltsch, “Genomic imprinting--the struggle of the genders at the molecular level,” Angew Chem Int Ed Engl, vol. 52, no. 51, Art. no. 51, 2013, doi: 10.1002/anie.201307005.
    5. 157. S. Muller et al., “Target recognition, RNA methylation activity and transcriptional regulation of the Dictyostelium discoideum Dnmt2-homologue (DnmA),” Nucleic Acids Res, vol. 41, no. 18, Art. no. 18, 2013, doi: 10.1093/nar/gkt634.
    6. 156. A. N. Siddique et al., “Targeted methylation and gene silencing of VEGF-A in human cells by using a designed Dnmt3a-Dnmt3L single-chain fusion protein with increased DNA methylation activity,” J Mol Biol, vol. 425, no. 3, Art. no. 3, 2013, doi: 10.1016/j.jmb.2012.11.038.
  10. 2012

    1. 155. R. F. Albu, M. Zacharias, T. P. Jurkowski, and A. Jeltsch, “DNA interaction of the CcrM DNA methyltransferase: a mutational and modeling study,” Chembiochem, vol. 13, no. 9, Art. no. 9, 2012, doi: 10.1002/cbic.201200082.
    2. 154. R. F. Albu, T. P. Jurkowski, and A. Jeltsch, “The Caulobacter crescentus DNA-(adenine-N6)-methyltransferase CcrM methylates DNA in a distributive manner,” Nucleic Acids Res, vol. 40, no. 4, Art. no. 4, 2012, doi: 10.1093/nar/gkr768.
    3. 153. P. Bashtrykov, S. Ragozin, and A. Jeltsch, “Mechanistic details of the DNA recognition by the Dnmt1 DNA methyltransferase,” FEBS Lett, vol. 586, no. 13, Art. no. 13, 2012, doi: 10.1016/j.febslet.2012.05.026.
    4. 152. P. Bashtrykov, G. Jankevicius, A. Smarandache, R. Z. Jurkowska, S. Ragozin, and A. Jeltsch, “Specificity of Dnmt1 for methylation of hemimethylated CpG sites resides in its catalytic domain,” Chem Biol, vol. 19, no. 5, Art. no. 5, 2012, doi: 10.1016/j.chembiol.2012.03.010.
    5. 151. M. Becker, S. Muller, W. Nellen, T. P. Jurkowski, A. Jeltsch, and A. E. Ehrenhofer-Murray, “Pmt1, a Dnmt2 homolog in Schizosaccharomyces pombe, mediates tRNA methylation in response to nutrient signaling,” Nucleic Acids Res, vol. 40, no. 22, Art. no. 22, 2012, doi: 10.1093/nar/gks956.
    6. 150. E. Y. Bonnist, K. Liebert, D. T. Dryden, A. Jeltsch, and A. C. Jones, “Using the fluorescence decay of 2-aminopurine to investigate conformational change in the recognition sequence of the EcoRV DNA-(adenine-N6)-methyltransferase on enzyme binding,” Biophys Chem, vol. 160, no. 1, Art. no. 1, 2012, doi: 10.1016/j.bpc.2011.09.001.
    7. 149. J. Fahy, A. Jeltsch, and P. B. Arimondo, “DNA methyltransferase inhibitors in cancer: a chemical and therapeutic patent overview and selected clinical studies,” Expert Opin Ther Pat, vol. 22, no. 12, Art. no. 12, 2012, doi: 10.1517/13543776.2012.729579.
    8. 148. M. Florea, S. Kudithipudi, A. Rei, M. J. Gonzalez-Alvarez, A. Jeltsch, and W. M. Nau, “A fluorescence-based supramolecular tandem assay for monitoring lysine methyltransferase activity in homogeneous solution,” Chemistry, vol. 18, no. 12, Art. no. 12, 2012, doi: 10.1002/chem.201103397.
    9. 147. L. Halby et al., “Rapid synthesis of new DNMT inhibitors derivatives of procainamide,” Chembiochem, vol. 13, no. 1, Art. no. 1, 2012, doi: 10.1002/cbic.201100522.
    10. 146. T. P. Jurkowski, R. Shanmugam, M. Helm, and A. Jeltsch, “Mapping the tRNA binding site on the surface of human DNMT2 methyltransferase,” Biochemistry, vol. 51, no. 22, Art. no. 22, 2012, doi: 10.1021/bi3002659.
    11. 145. S. Kudithipudi, A. Dhayalan, A. F. Kebede, and A. Jeltsch, “The SET8 H4K20 protein lysine methyltransferase has a long recognition sequence covering seven amino acid residues,” Biochimie, vol. 94, no. 11, Art. no. 11, 2012, doi: 10.1016/j.biochi.2012.04.024.
    12. 144. D. Kutscher, A. Pingoud, A. Jeltsch, and G. Meiss, “Identification of ICAD-derived peptides capable of inhibiting caspase-activated DNase,” FEBS J, vol. 279, no. 16, Art. no. 16, 2012, doi: 10.1111/j.1742-4658.2012.08673.x.
    13. 143. A. Rajavelu, R. Z. Jurkowska, J. Fritz, and A. Jeltsch, “Function and disruption of DNA methyltransferase 3a cooperative DNA binding and nucleoprotein filament formation,” Nucleic Acids Res, vol. 40, no. 2, Art. no. 2, 2012, doi: 10.1093/nar/gkr753.
    14. 142. C. Voelcker-Rehage, A. Jeltsch, B. Godde, and U. M. Staudinger, “Comt Polymorphisms Influence the Association between Physical and Cognitive Fitness in Older Adults,” Gerontologist, vol. 52, pp. 299–299, 2012, [Online]. Available: /brokenurl#<Go to ISI>://000312888202549.
  11. 2011

    1. 141. I. Bock, S. Kudithipudi, R. Tamas, G. Kungulovski, A. Dhayalan, and A. Jeltsch, “Application of Celluspots peptide arrays for the analysis of the binding specificity of epigenetic reading domains to modified histone tails,” BMC Biochem, vol. 12, p. 48, 2011, doi: 10.1186/1471-2091-12-48.
    2. 140. I. Bock, A. Dhayalan, S. Kudithipudi, O. Brandt, P. Rathert, and A. Jeltsch, “Detailed specificity analysis of antibodies binding to modified histone tails with peptide arrays,” Epigenetics, vol. 6, no. 2, Art. no. 2, 2011, doi: 10.4161/epi.6.2.13837.
    3. 139. A. Ceccaldi et al., “C5-DNA methyltransferase inhibitors: from screening to effects on zebrafish embryo development,” Chembiochem, vol. 12, no. 9, Art. no. 9, 2011, doi: 10.1002/cbic.201100130.
    4. 138. A. Dhayalan, S. Kudithipudi, P. Rathert, and A. Jeltsch, “Specificity analysis-based identification of new methylation targets of the SET7/9 protein lysine methyltransferase,” Chem Biol, vol. 18, no. 1, Art. no. 1, 2011, doi: 10.1016/j.chembiol.2010.11.014.
    5. 137. A. Dhayalan et al., “The ATRX-ADD domain binds to H3 tail peptides and reads the combined methylation state of K4 and K9,” Hum Mol Genet, vol. 20, no. 11, Art. no. 11, 2011, doi: 10.1093/hmg/ddr107.
    6. 136. A. Jeltsch and W. Fischle, “Molecular epigenetics: connecting human biology and disease with little marks,” Chembiochem, vol. 12, no. 2, Art. no. 2, 2011, doi: 10.1002/cbic.201000779.
    7. 135. A. Jeltsch, “Epigenetics Europe conference. Munich, Germany, 8-9 September 2011,” Epigenomics, vol. 3, no. 6, Art. no. 6, 2011, doi: 10.2217/epi.11.95.
    8. 134. R. Z. Jurkowska et al., “Oligomerization and binding of the Dnmt3a DNA methyltransferase to parallel DNA molecules: heterochromatic localization and role of Dnmt3L,” J Biol Chem, vol. 286, no. 27, Art. no. 27, 2011, doi: 10.1074/jbc.M111.254987.
    9. 133. R. Z. Jurkowska, A. Ceccaldi, Y. Zhang, P. B. Arimondo, and A. Jeltsch, “DNA methyltransferase assays,” Methods Mol Biol, vol. 791, pp. 157–77, 2011, doi: 10.1007/978-1-61779-316-5_13.
    10. 132. R. Z. Jurkowska, T. P. Jurkowski, and A. Jeltsch, “Structure and function of mammalian DNA methyltransferases,” Chembiochem, vol. 12, no. 2, Art. no. 2, 2011, doi: 10.1002/cbic.201000195.
    11. 131. R. Z. Jurkowska, A. N. Siddique, T. P. Jurkowski, and A. Jeltsch, “Approaches to enzyme and substrate design of the murine Dnmt3a DNA methyltransferase,” Chembiochem, vol. 12, no. 10, Art. no. 10, 2011, doi: 10.1002/cbic.201000673.
    12. 130. T. P. Jurkowski and A. Jeltsch, “On the evolutionary origin of eukaryotic DNA methyltransferases and Dnmt2,” PLoS One, vol. 6, no. 11, Art. no. 11, 2011, doi: 10.1371/journal.pone.0028104.
    13. 129. T. P. Jurkowski and A. Jeltsch, “Burning off DNA methylation: new evidence for oxygen-dependent DNA demethylation,” Chembiochem, vol. 12, no. 17, Art. no. 17, 2011, doi: 10.1002/cbic.201100549.
    14. 128. B. Z. Li et al., “Histone tails regulate DNA methylation by allosterically activating de novo methyltransferase,” Cell Res, vol. 21, no. 8, Art. no. 8, 2011, doi: 10.1038/cr.2011.92.
    15. 127. A. Rajavelu, Z. Tulyasheva, R. Jaiswal, A. Jeltsch, and N. Kuhnert, “The inhibition of the mammalian DNA methyltransferase 3a (Dnmt3a) by dietary black tea and coffee polyphenols,” BMC Biochem, vol. 12, p. 16, 2011, doi: 10.1186/1471-2091-12-16.
    16. 126. A. N. Siddique, R. Z. Jurkowska, T. P. Jurkowski, and A. Jeltsch, “Auto-methylation of the mouse DNA-(cytosine C5)-methyltransferase Dnmt3a at its active site cysteine residue,” FEBS J, vol. 278, no. 12, Art. no. 12, 2011, doi: 10.1111/j.1742-4658.2011.08121.x.
  12. 2010

    1. 125. S. Chahar, H. Elsawy, S. Ragozin, and A. Jeltsch, “Changing the DNA recognition specificity of the EcoDam DNA-(adenine-N6)-methyltransferase by directed evolution,” J Mol Biol, vol. 395, no. 1, Art. no. 1, 2010, doi: 10.1016/j.jmb.2009.09.027.
    2. 124. C. Champion et al., “Mechanistic insights on the inhibition of c5 DNA methyltransferases by zebularine,” PLoS One, vol. 5, no. 8, Art. no. 8, 2010, doi: 10.1371/journal.pone.0012388.
    3. 123. A. Dhayalan et al., “The Dnmt3a PWWP domain reads histone 3 lysine 36 trimethylation and guides DNA methylation,” J Biol Chem, vol. 285, no. 34, Art. no. 34, 2010, doi: 10.1074/jbc.M109.089433.
    4. 122. A. Jeltsch, “Molecular biology. Phylogeny of methylomes,” Science, vol. 328, no. 5980, Art. no. 5980, 2010, doi: 10.1126/science.1190738.
    5. 121. R. Z. Jurkowska and A. Jeltsch, “Silencing of gene expression by targeted DNA methylation: concepts and approaches,” Methods Mol Biol, vol. 649, pp. 149–61, 2010, doi: 10.1007/978-1-60761-753-2_9.
    6. 120. R. Metivier et al., “Cyclical DNA methylation of a transcriptionally active promoter (vol 452, pg 45, 2008),” Nature, vol. 463, no. 7279, Art. no. 7279, 2010, doi: 10.1038/nature08661.
    7. 119. C. Rohde, Y. Zhang, R. Reinhardt, and A. Jeltsch, “BISMA--fast and accurate bisulfite sequencing data analysis of individual clones from unique and repetitive sequences,” BMC Bioinformatics, vol. 11, p. 230, 2010, doi: 10.1186/1471-2105-11-230.
    8. 118. Y. Zhang and A. Jeltsch, “The application of next generation sequencing in DNA methylation analysis,” Genes (Basel), vol. 1, no. 1, Art. no. 1, 2010, doi: 10.3390/genes1010085.
    9. 117. Y. Zhang et al., “Chromatin methylation activity of Dnmt3a and Dnmt3a/3L is guided by interaction of the ADD domain with the histone H3 tail,” Nucleic Acids Res, vol. 38, no. 13, Art. no. 13, 2010, doi: 10.1093/nar/gkq147.
  13. 2009

    1. 116. A. Dhayalan, E. Dimitrova, P. Rathert, and A. Jeltsch, “A continuous protein methyltransferase (G9a) assay for enzyme activity measurement and inhibitor screening,” J Biomol Screen, vol. 14, no. 9, Art. no. 9, 2009, doi: 10.1177/1087057109345528.
    2. 115. H. Elsawy, S. Podobinschi, S. Chahar, and A. Jeltsch, “Transition from EcoDam to T4Dam DNA recognition mechanism without loss of activity and specificity,” Chembiochem, vol. 10, no. 15, Art. no. 15, 2009, doi: 10.1002/cbic.200900441.
    3. 114. T. Gao et al., “The ankyrin repeat domain of Huntingtin interacting protein 14 contains a surface aromatic cage, a potential site for methyl-lysine binding,” Proteins, vol. 76, no. 3, Art. no. 3, 2009, doi: 10.1002/prot.22452.
    4. 113. D. V. Maltseva, A. A. Baykov, A. Jeltsch, and E. S. Gromova, “Impact of 7,8-dihydro-8-oxoguanine on methylation of the CpG site by Dnmt3a,” Biochemistry, vol. 48, no. 6, Art. no. 6, 2009, doi: 10.1021/bi801947f.
    5. 112. V. Pingoud et al., “On the divalent metal ion dependence of DNA cleavage by restriction endonucleases of the EcoRI family,” J Mol Biol, vol. 393, no. 1, Art. no. 1, 2009, doi: 10.1016/j.jmb.2009.08.011.
    6. 111. C. Rohde, Y. Zhang, H. Stamerjohanns, K. Hecher, R. Reinhardt, and A. Jeltsch, “New clustering module in BDPC bisulfite sequencing data presentation and compilation web application for DNA methylation analyses,” Biotechniques, vol. 47, no. 3, Art. no. 3, 2009, doi: 10.2144/000113196.
    7. 110. Y. Zhang et al., “DNA methylation analysis of chromosome 21 gene promoters at single base pair and single allele resolution,” PLoS Genet, vol. 5, no. 3, Art. no. 3, 2009, doi: 10.1371/journal.pgen.1000438.
    8. 109. Y. Zhang, C. Rohde, R. Reinhardt, C. Voelcker-Rehage, and A. Jeltsch, “Non-imprinted allele-specific DNA methylation on human autosomes,” Genome Biol, vol. 10, no. 12, Art. no. 12, 2009, doi: 10.1186/gb-2009-10-12-r138.
    9. 108. Y. Zhang et al., “DNA methylation analysis by bisulfite conversion, cloning, and sequencing of individual clones,” Methods Mol Biol, vol. 507, pp. 177–87, 2009, doi: 10.1007/978-1-59745-522-0_14.
  14. 2008

    1. 107. A. Dhayalan et al., “Mapping of protein-protein interaction sites by the ‘absence of interference’ approach,” J Mol Biol, vol. 376, no. 4, Art. no. 4, 2008, doi: 10.1016/j.jmb.2007.12.032.
    2. 106. A. Jeltsch and P. Rathert, “Putting the pieces together: histone H2B ubiquitylation directly stimulates histone H3K79 methylation,” Chembiochem, vol. 9, no. 14, Art. no. 14, 2008, doi: 10.1002/cbic.200800414.
    3. 105. A. Jeltsch, “Reading and writing DNA methylation,” Nat Struct Mol Biol, vol. 15, no. 10, Art. no. 10, 2008, doi: 10.1038/nsmb1008-1003.
    4. 104. R. Z. Jurkowska et al., “Formation of nucleoprotein filaments by mammalian DNA methyltransferase Dnmt3a in complex with regulator Dnmt3L,” Nucleic Acids Res, vol. 36, no. 21, Art. no. 21, 2008, doi: 10.1093/nar/gkn747.
    5. 103. T. P. Jurkowski et al., “Human DNMT2 methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalytic mechanism,” RNA, vol. 14, no. 8, Art. no. 8, 2008, doi: 10.1261/rna.970408.
    6. 102. K. Liebert and A. Jeltsch, “Detection and quantitation of the activity of DNA methyltransferases using a biotin/avidin microplate assay,” Methods Mol Biol, vol. 418, pp. 149–56, 2008, doi: 10.1007/978-1-59745-579-4_13.
    7. 101. R. Metivier et al., “Cyclical DNA methylation of a transcriptionally active promoter,” Nature, vol. 452, no. 7183, Art. no. 7183, 2008, doi: 10.1038/nature06544.
    8. 100. P. Rathert et al., “Protein lysine methyltransferase G9a acts on non-histone targets,” Nat Chem Biol, vol. 4, no. 6, Art. no. 6, 2008, doi: 10.1038/nchembio.88.
    9. 99. P. Rathert, X. Zhang, C. Freund, X. Cheng, and A. Jeltsch, “Analysis of the substrate specificity of the Dim-5 histone lysine methyltransferase using peptide arrays,” Chem Biol, vol. 15, no. 1, Art. no. 1, 2008, doi: 10.1016/j.chembiol.2007.11.013.
    10. 98. P. Rathert, A. Dhayalan, H. Ma, and A. Jeltsch, “Specificity of protein lysine methyltransferases and methods for detection of lysine methylation of non-histone proteins,” Mol Biosyst, vol. 4, no. 12, Art. no. 12, 2008, doi: 10.1039/b811673c.
    11. 97. C. Rohde, Y. Zhang, T. P. Jurkowski, H. Stamerjohanns, R. Reinhardt, and A. Jeltsch, “Bisulfite sequencing Data Presentation and Compilation (BDPC) web server--a useful tool for DNA methylation analysis,” Nucleic Acids Res, vol. 36, no. 5, Art. no. 5, 2008, doi: 10.1093/nar/gkn083.
    12. 96. B. T. F. van der Gun et al., “Persistent downregulation of the pancarcinoma-associated epithelial cell adhesion molecule via active intranuclear methylation,” Int J Cancer, vol. 123, no. 2, Art. no. 2, 2008, doi: 10.1002/ijc.23476.
  15. 2007

    1. 95. R. Gallais et al., “Deoxyribonucleic acid methyl transferases 3a and 3b associate with the nuclear orphan receptor COUP-TFI during gene activation,” Mol Endocrinol, vol. 21, no. 9, Art. no. 9, 2007, doi: 10.1210/me.2006-0490.
    2. 94. R. Goyal, P. Rathert, H. Laser, H. Gowher, and A. Jeltsch, “Phosphorylation of serine-515 activates the Mammalian maintenance methyltransferase Dnmt1,” Epigenetics, vol. 2, no. 3, Art. no. 3, 2007, doi: 10.4161/epi.2.3.4768.
    3. 93. A. Jeltsch, R. Z. Jurkowska, T. P. Jurkowski, K. Liebert, P. Rathert, and M. Schlickenrieder, “Application of DNA methyltransferases in targeted DNA methylation,” Appl Microbiol Biotechnol, vol. 75, no. 6, Art. no. 6, 2007, doi: 10.1007/s00253-007-0966-0.
    4. 92. D. Jia, R. Z. Jurkowska, X. Zhang, A. Jeltsch, and X. Cheng, “Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation,” Nature, vol. 449, no. 7159, Art. no. 7159, 2007, doi: 10.1038/nature06146.
    5. 91. T. P. Jurkowski, N. Anspach, L. Kulishova, W. Nellen, and A. Jeltsch, “The M.EcoRV DNA-(adenine N6)-methyltransferase uses DNA bending for recognition of an expanded EcoDam recognition site,” J Biol Chem, vol. 282, no. 51, Art. no. 51, 2007, doi: 10.1074/jbc.M706933200.
    6. 90. F. Li et al., “Chimeric DNA methyltransferases target DNA methylation to specific DNA sequences and repress expression of target genes,” Nucleic Acids Res, vol. 35, no. 1, Art. no. 1, 2007, doi: 10.1093/nar/gkl1035.
    7. 89. K. Liebert, J. R. Horton, S. Chahar, M. Orwick, X. Cheng, and A. Jeltsch, “Two alternative conformations of S-adenosyl-L-homocysteine bound to Escherichia coli DNA adenine methyltransferase and the implication of conformational changes in regulating the catalytic cycle,” J Biol Chem, vol. 282, no. 31, Art. no. 31, 2007, doi: 10.1074/jbc.M700926200.
    8. 88. P. Rathert, X. Cheng, and A. Jeltsch, “Continuous enzymatic assay for histone lysine methyltransferases,” Biotechniques, vol. 43, no. 5, Art. no. 5, 2007, doi: 10.2144/000112623.
    9. 87. P. Rathert et al., “Reversible inactivation of the CG specific SssI DNA (cytosine-C5)-methyltransferase with a photocleavable protecting group,” Chembiochem, vol. 8, no. 2, Art. no. 2, 2007, doi: 10.1002/cbic.200600358.
  16. 2006

    1. 86. H. Gowher et al., “Mutational analysis of the catalytic domain of the murine Dnmt3a DNA-(cytosine C5)-methyltransferase,” J Mol Biol, vol. 357, no. 3, Art. no. 3, 2006, doi: 10.1016/j.jmb.2006.01.035.
    2. 85. R. Goyal, R. Reinhardt, and A. Jeltsch, “Accuracy of DNA methylation pattern preservation by the Dnmt1 methyltransferase,” Nucleic Acids Res, vol. 34, no. 4, Art. no. 4, 2006, doi: 10.1093/nar/gkl002.
    3. 84. E. Gromova et al., “Impact of benzoapyrene diol epoxide-DNA adducts on DNA methylation,” Febs Journal, vol. 273, pp. 187–188, 2006, [Online]. Available: /brokenurl#<Go to ISI>://000238914001230.
    4. 83. J. R. Horton, K. Liebert, M. Bekes, A. Jeltsch, and X. Cheng, “Structure and substrate recognition of the Escherichia coli DNA adenine methyltransferase,” J Mol Biol, vol. 358, no. 2, Art. no. 2, 2006, doi: 10.1016/j.jmb.2006.02.028.
    5. 82. A. Jeltsch, “On the enzymatic properties of Dnmt1: specificity, processivity, mechanism of linear diffusion and allosteric regulation of the enzyme,” Epigenetics, vol. 1, no. 2, Art. no. 2, 2006, doi: 10.4161/epi.1.2.2767.
    6. 81. A. Jeltsch, W. Nellen, and F. Lyko, “Two substrates are better than one: dual specificities for Dnmt2 methyltransferases,” Trends Biochem Sci, vol. 31, no. 6, Art. no. 6, 2006, doi: 10.1016/j.tibs.2006.04.005.
    7. 80. A. Jeltsch, “Molecular enzymology of mammalian DNA methyltransferases,” Curr Top Microbiol Immunol, vol. 301, pp. 203–25, 2006, doi: 10.1007/3-540-31390-7_7.
    8. 79. A. Jeltsch, J. Walter, R. Reinhardt, and M. Platzer, “German human methylome project started,” Cancer Res, vol. 66, no. 14, Art. no. 14, 2006, doi: 10.1158/0008-5472.CAN-06-1071.
    9. 78. Z. H. Xie et al., “Mutations in DNA methyltransferase DNMT3B in ICF syndrome affect its regulation by DNMT3L,” Hum Mol Genet, vol. 15, no. 9, Art. no. 9, 2006, doi: 10.1093/hmg/ddl059.
  17. 2005

    1. 77. K. Eisenschmidt et al., “Developing a programmed restriction endonuclease for highly specific DNA cleavage,” Nucleic Acids Res, vol. 33, no. 22, Art. no. 22, 2005, doi: 10.1093/nar/gki1009.
    2. 76. H. Gowher, C. J. Stockdale, R. Goyal, H. Ferreira, T. Owen-Hughes, and A. Jeltsch, “De novo methylation of nucleosomal DNA by the mammalian Dnmt1 and Dnmt3A DNA methyltransferases,” Biochemistry, vol. 44, no. 29, Art. no. 29, 2005, doi: 10.1021/bi047634t.
    3. 75. H. Gowher, K. Liebert, A. Hermann, G. Xu, and A. Jeltsch, “Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L,” J Biol Chem, vol. 280, no. 14, Art. no. 14, 2005, doi: 10.1074/jbc.M413412200.
    4. 74. H. Gowher, X. Zhang, X. Cheng, and A. Jeltsch, “Avidin plate assay system for enzymatic characterization of a histone lysine methyltransferase,” Anal Biochem, vol. 342, no. 2, Art. no. 2, 2005, doi: 10.1016/j.ab.2005.04.028.
    5. 73. V. Handa and A. Jeltsch, “Profound flanking sequence preference of Dnmt3a and Dnmt3b mammalian DNA methyltransferases shape the human epigenome,” J Mol Biol, vol. 348, no. 5, Art. no. 5, 2005, doi: 10.1016/j.jmb.2005.02.044.
    6. 72. J. R. Horton, K. Liebert, S. Hattman, A. Jeltsch, and X. Cheng, “Transition from nonspecific to specific DNA interactions along the substrate-recognition pathway of dam methyltransferase,” Cell, vol. 121, no. 3, Art. no. 3, 2005, doi: 10.1016/j.cell.2005.02.021.
  18. 2004

    1. 71. Y. Z. Ge et al., “Chromatin targeting of de novo DNA methyltransferases by the PWWP domain,” J Biol Chem, vol. 279, no. 24, Art. no. 24, 2004, doi: 10.1074/jbc.M312296200.
    2. 70. H. Gowher and A. Jeltsch, “Mechanism of inhibition of DNA methyltransferases by cytidine analogs in cancer therapy,” Cancer Biol Ther, vol. 3, no. 11, Art. no. 11, 2004, doi: 10.4161/cbt.3.11.1308.
    3. 69. V. Handa and A. Jeltsch, “Anomalous mobility of polymerase chain reaction products after bisulfite treatment of DNA,” Anal Biochem, vol. 333, no. 1, Art. no. 1, 2004, doi: 10.1016/j.ab.2004.06.018.
    4. 68. A. Hermann, H. Gowher, and A. Jeltsch, “Biochemistry and biology of mammalian DNA methyltransferases,” Cell Mol Life Sci, vol. 61, no. 19–20, Art. no. 19–20, 2004, doi: 10.1007/s00018-004-4201-1.
    5. 67. A. Hermann, R. Goyal, and A. Jeltsch, “The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites,” J Biol Chem, vol. 279, no. 46, Art. no. 46, 2004, doi: 10.1074/jbc.M403427200.
    6. 66. K. Liebert, A. Hermann, M. Schlickenrieder, and A. Jeltsch, “Stopped-flow and mutational analysis of base flipping by the Escherichia coli Dam DNA-(adenine-N6)-methyltransferase,” J Mol Biol, vol. 341, no. 2, Art. no. 2, 2004, doi: 10.1016/j.jmb.2004.05.033.
  19. 2003

    1. 65. A. Hermann and A. Jeltsch, “Methylation sensitivity of restriction enzymes interacting with GATC sites,” Biotechniques, vol. 34, no. 5, Art. no. 5, 2003, doi: 10.2144/03345bm05.
    2. 64. A. Hermann, S. Schmitt, and A. Jeltsch, “The human Dnmt2 has residual DNA-(cytosine-C5) methyltransferase activity,” J Biol Chem, vol. 278, no. 34, Art. no. 34, 2003, doi: 10.1074/jbc.M305448200.
    3. 63. A. Humeny, C. Beck, C. M. Becker, and A. Jeltsch, “Detection and analysis of enzymatic DNA methylation of oligonucleotide substrates by matrix-assisted laser desorption ionization time-of-flight mass spectrometry,” Anal Biochem, vol. 313, no. 1, Art. no. 1, 2003, doi: 10.1016/s0003-2697(02)00568-7.
    4. 62. A. Jeltsch, “Maintenance of species identity and controlling speciation of bacteria: a new function for restriction/modification systems?,” Gene, vol. 317, no. 1–2, Art. no. 1–2, 2003, doi: 10.1016/s0378-1119(03)00652-8.
    5. 61. T. Lanio, A. Jeltsch, and A. Pingoud, “High-throughput purification of polyHis-tagged recombinant fusion proteins,” Methods Mol Biol, vol. 205, pp. 199–203, 2003, doi: 10.1385/1-59259-301-1:199.
    6. 60. S. Reither, F. Li, H. Gowher, and A. Jeltsch, “Catalytic mechanism of DNA-(cytosine-C5)-methyltransferases revisited: covalent intermediate formation is not essential for methyl group transfer by the murine Dnmt3a enzyme,” J Mol Biol, vol. 329, no. 4, Art. no. 4, 2003, doi: 10.1016/s0022-2836(03)00509-6.
    7. 59. R. J. Roberts et al., “A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes,” Nucleic Acids Res, vol. 31, no. 7, Art. no. 7, 2003, doi: 10.1093/nar/gkg274.
    8. 58. A. Spyridaki et al., “Structural and biochemical characterization of a new Mg(2+) binding site near Tyr94 in the restriction endonuclease PvuII,” J Mol Biol, vol. 331, no. 2, Art. no. 2, 2003, doi: 10.1016/s0022-2836(03)00692-2.
  20. 2002

    1. 57. C. Beck and A. Jeltsch, “Probing the DNA interface of the EcoRV DNA-(adenine-N6)-methyltransferase by site-directed mutagenesis, fluorescence spectroscopy, and UV cross-linking,” Biochemistry, vol. 41, no. 48, Art. no. 48, 2002, doi: 10.1021/bi025979a.
    2. 56. K. Eisenschmidt, T. Lanio, A. Jeltsch, and A. Pingoud, “A fluorimetric assay for on-line detection of DNA cleavage by restriction endonucleases,” J Biotechnol, vol. 96, no. 2, Art. no. 2, 2002, doi: 10.1016/s0168-1656(02)00029-9.
    3. 55. M. Fatemi, A. Hermann, H. Gowher, and A. Jeltsch, “Dnmt3a and Dnmt1 functionally cooperate during de novo methylation of DNA,” Eur J Biochem, vol. 269, no. 20, Art. no. 20, 2002, doi: 10.1046/j.1432-1033.2002.03198.x.
    4. 54. H. Gowher and A. Jeltsch, “Molecular enzymology of the catalytic domains of the Dnmt3a and Dnmt3b DNA methyltransferases,” J Biol Chem, vol. 277, no. 23, Art. no. 23, 2002, doi: 10.1074/jbc.M202148200.
    5. 53. A. Jeltsch, “Beyond Watson and Crick: DNA methylation and molecular enzymology of DNA methyltransferases,” Chembiochem, vol. 3, no. 4, Art. no. 4, 2002, doi: 10.1002/1439-7633(20020402)3:4<274::AID-CBIC274>3.0.CO;2-S.
    6. 52. A. Jeltsch and T. Lanio, “Site-directed mutagenesis by polymerase chain reaction,” Methods Mol Biol, vol. 182, pp. 85–94, 2002, doi: 10.1385/1-59259-194-9:085.
    7. 51. S. Reither and A. Jeltsch, “Specificity of DNA triple helix formation analyzed by a FRET assay,” BMC Biochem, vol. 3, p. 27, 2002, doi: 10.1186/1471-2091-3-27.
    8. 50. S. Urig et al., “The Escherichia coli dam DNA methyltransferase modifies DNA in a highly processive reaction,” J Mol Biol, vol. 319, no. 5, Art. no. 5, 2002, doi: 10.1016/S0022-2836(02)00371-6.
  21. 2001

    1. 49. C. Beck, S. Cranz, M. Solmaz, M. Roth, and A. Jeltsch, “How does a DNA interacting enzyme change its specificity during molecular evolution? A site-directed mutagenesis study at the DNA binding site of the DNA-(adenine-N6)-methyltransferase EcoRV,” Biochemistry, vol. 40, no. 37, Art. no. 37, 2001, [Online]. Available: http://www.ncbi.nlm.nih.gov/pubmed/11551190.
    2. 48. M. Fatemi, A. Hermann, S. Pradhan, and A. Jeltsch, “The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA,” J Mol Biol, vol. 309, no. 5, Art. no. 5, 2001, doi: 10.1006/jmbi.2001.4709.
    3. 47. H. Gowher and A. Jeltsch, “Enzymatic properties of recombinant Dnmt3a DNA methyltransferase from mouse: the enzyme modifies DNA in a non-processive manner and also methylates non-CpG correction of non-CpA sites,” J Mol Biol, vol. 309, no. 5, Art. no. 5, 2001, doi: 10.1006/jmbi.2001.4710.
    4. 46. H. Gowher, K. C. Ehrlich, and A. Jeltsch, “DNA from Aspergillus flavus contains 5-methylcytosine,” FEMS Microbiol Lett, vol. 205, no. 1, Art. no. 1, 2001, doi: 10.1111/j.1574-6968.2001.tb10939.x.
    5. 45. A. Jeltsch, “The cytosine N4-methyltransferase M.PvuII also modifies adenine residues,” Biol Chem, vol. 382, no. 4, Art. no. 4, 2001, doi: 10.1515/BC.2001.084.
    6. 44. A. Jeltsch and A. M. Pingoud, “Methods for determining activity and specificity of DNA binding and DNA cleavage by class II restriction endonucleases,” Methods Mol Biol, vol. 160, pp. 287–308, 2001, doi: 10.1385/1-59259-233-3:287.
    7. 43. A. Pingoud and A. Jeltsch, “Structure and function of type II restriction endonucleases,” Nucleic Acids Res, vol. 29, no. 18, Art. no. 18, 2001, doi: 10.1093/nar/29.18.3705.
    8. 42. M. Roth and A. Jeltsch, “Changing the target base specificity of the EcoRV DNA methyltransferase by rational de novo protein-design,” Nucleic Acids Res, vol. 29, no. 15, Art. no. 15, 2001, doi: 10.1093/nar/29.15.3137.
  22. 2000

    1. 41. T. Friedrich, M. Fatemi, H. Gowhar, O. Leismann, and A. Jeltsch, “Specificity of DNA binding and methylation by the M.FokI DNA methyltransferase,” Biochim Biophys Acta, vol. 1480, no. 1–2, Art. no. 1–2, 2000, doi: 10.1016/s0167-4838(00)00065-0.
    2. 40. H. Gowher, O. Leismann, and A. Jeltsch, “DNA of Drosophila melanogaster contains 5-methylcytosine,” EMBO J, vol. 19, no. 24, Art. no. 24, 2000, doi: 10.1093/emboj/19.24.6918.
    3. 39. H. Gowher and A. Jeltsch, “Molecular enzymology of the EcoRV DNA-(Adenine-N (6))-methyltransferase: kinetics of DNA binding and bending, kinetic mechanism and linear diffusion of the enzyme on DNA,” J Mol Biol, vol. 303, no. 1, Art. no. 1, 2000, doi: 10.1006/jmbi.2000.4127.
    4. 38. T. Lanio, A. Jeltsch, and A. Pingoud, “On the possibilities and limitations of rational protein design to expand the specificity of restriction enzymes: a case study employing EcoRV as the target,” Protein Eng, vol. 13, no. 4, Art. no. 4, 2000, doi: 10.1093/protein/13.4.275.
    5. 37. T. Lanio, A. Jeltsch, and A. Pingoud, “Automated purification of His6-tagged proteins allows exhaustive screening of libraries generated by random mutagenesis,” Biotechniques, vol. 29, no. 2, Art. no. 2, 2000, doi: 10.2144/00292rr01.
    6. 36. M. Roth and A. Jeltsch, “Biotin-avidin microplate assay for the quantitative analysis of enzymatic methylation of DNA by DNA methyltransferases,” Biol Chem, vol. 381, no. 3, Art. no. 3, 2000, doi: 10.1515/BC.2000.035.
  23. 1999

    1. 35. A. Jeltsch, M. Roth, and T. Friedrich, “Mutational analysis of target base flipping by the EcoRV adenine-N6 DNA methyltransferase,” J Mol Biol, vol. 285, no. 3, Art. no. 3, 1999, doi: 10.1006/jmbi.1998.2389.
    2. 34. A. Jeltsch, “Circular permutations in the molecular evolution of DNA methyltransferases,” J Mol Evol, vol. 49, no. 1, Art. no. 1, 1999, doi: 10.1007/pl00006529.
    3. 33. A. Jeltsch, F. Christ, M. Fatemi, and M. Roth, “On the substrate specificity of DNA methyltransferases. adenine-N6 DNA methyltransferases also modify cytosine residues at position N4,” J Biol Chem, vol. 274, no. 28, Art. no. 28, 1999, doi: 10.1074/jbc.274.28.19538.
    4. 32. G. Sasnauskas, A. Jeltsch, A. Pingoud, and V. Siksnys, “Plasmid DNA cleavage by MunI restriction enzyme: single-turnover and steady-state kinetic analysis,” Biochemistry, vol. 38, no. 13, Art. no. 13, 1999, doi: 10.1021/bi982456n.
  24. 1998

    1. 31. T. Friedrich, M. Roth, S. Helm-Kruse, and A. Jeltsch, “Functional mapping of the EcoRV DNA methyltransferase by random mutagenesis and screening for catalytically inactive mutants,” Biol Chem, vol. 379, no. 4–5, Art. no. 4–5, 1998, doi: 10.1515/bchm.1998.379.4-5.475.
    2. 30. A. Jeltsch, “Flexibility of DNA in complex with proteins deduced from the distribution of bending angles observed by scanning force microscopy,” Biophys Chem, vol. 74, no. 1, Art. no. 1, 1998, doi: 10.1016/s0301-4622(98)00163-x.
    3. 29. A. Jeltsch and A. Pingoud, “Kinetic characterization of linear diffusion of the restriction endonuclease EcoRV on DNA,” Biochemistry, vol. 37, no. 8, Art. no. 8, 1998, doi: 10.1021/bi9719206.
    4. 28. A. Jeltsch, T. Friedrich, and M. Roth, “Kinetics of methylation and binding of DNA by the EcoRV adenine-N6 methyltransferase,” J Mol Biol, vol. 275, no. 5, Art. no. 5, 1998, doi: 10.1006/jmbi.1997.1492.
    5. 27. T. Lanio and A. Jeltsch, “PCR-based random mutagenesis method using spiked oligonucleotides to randomize selected parts of a gene without any wild-type background,” Biotechniques, vol. 25, no. 6, Art. no. 6, 1998, doi: 10.2144/98256bm06.
    6. 26. T. Lanio, A. Jeltsch, and A. Pingoud, “Towards the design of rare cutting restriction endonucleases: using directed evolution to generate variants of EcoRV differing in their substrate specificity by two orders of magnitude,” J Mol Biol, vol. 283, no. 1, Art. no. 1, 1998, doi: 10.1006/jmbi.1998.2088.
    7. 25. O. Leismann, M. Roth, T. Friedrich, W. Wende, and A. Jeltsch, “The Flavobacterium okeanokoites adenine-N6-specific DNA-methyltransferase M.FokI is a tandem enzyme of two independent domains with very different kinetic properties,” Eur J Biochem, vol. 251, no. 3, Art. no. 3, 1998, doi: 10.1046/j.1432-1327.1998.2510899.x.
    8. 24. M. Roth, S. Helm-Kruse, T. Friedrich, and A. Jeltsch, “Functional roles of conserved amino acid residues in DNA methyltransferases investigated by site-directed mutagenesis of the EcoRV adenine-N6-methyltransferase,” J Biol Chem, vol. 273, no. 28, Art. no. 28, 1998, doi: 10.1074/jbc.273.28.17333.
    9. 23. S. Schottler, C. Wenz, T. Lanio, A. Jeltsch, and A. Pingoud, “Protein engineering of the restriction endonuclease EcoRV--structure-guided design of enzyme variants that recognize the base pairs flanking the recognition site,” Eur J Biochem, vol. 258, no. 1, Art. no. 1, 1998, doi: 10.1046/j.1432-1327.1998.2580184.x.
    10. 22. C. Schulze, A. Jeltsch, I. Franke, C. Urbanke, and A. Pingoud, “Crosslinking the EcoRV restriction endonuclease across the DNA-binding site reveals transient intermediates and conformational changes of the enzyme during DNA binding and catalytic turnover,” EMBO J, vol. 17, no. 22, Art. no. 22, 1998, doi: 10.1093/emboj/17.22.6757.
    11. 21. F. Stahl, W. Wende, C. Wenz, A. Jeltsch, and A. Pingoud, “Intra- vs intersubunit communication in the homodimeric restriction enzyme EcoRV: Thr 37 and Lys 38 involved in indirect readout are only important for the catalytic activity of their own subunit,” Biochemistry, vol. 37, no. 16, Art. no. 16, 1998, doi: 10.1021/bi973025s.
    12. 20. F. Stahl, W. Wende, A. Jeltsch, and A. Pingoud, “The mechanism of DNA cleavage by the type II restriction enzyme EcoRV: Asp36 is not directly involved in DNA cleavage but serves to couple indirect readout to catalysis,” Biol Chem, vol. 379, no. 4–5, Art. no. 4–5, 1998, doi: 10.1515/bchm.1998.379.4-5.467.
  25. 1997

    1. 19. D. H. Groll, A. Jeltsch, U. Selent, and A. Pingoud, “Does the restriction endonuclease EcoRV employ a two-metal-Ion mechanism for DNA cleavage?,” Biochemistry, vol. 36, no. 38, Art. no. 38, 1997, doi: 10.1021/bi9705826.
    2. 18. A. Pingoud and A. Jeltsch, “Recognition and cleavage of DNA by type-II restriction endonucleases,” Eur J Biochem, vol. 246, no. 1, Art. no. 1, 1997, doi: 10.1111/j.1432-1033.1997.t01-6-00001.x.
  26. 1996

    1. 17. A. Jeltsch, T. Sobotta, and A. Pingoud, “Structure prediction of the EcoRV DNA methyltransferase based on mutant profiling, secondary structure analysis, comparison with known structures of methyltransferases and isolation of catalytically inactive single mutants,” Protein Eng, vol. 9, no. 5, Art. no. 5, 1996, doi: 10.1093/protein/9.5.413.
    2. 16. A. Jeltsch and A. Pingoud, “Horizontal gene transfer contributes to the wide distribution and evolution of type II restriction-modification systems,” J Mol Evol, vol. 42, no. 2, Art. no. 2, 1996, doi: 10.1007/BF02198833.
    3. 15. A. Jeltsch, C. Wenz, W. Wende, U. Selent, and A. Pingoud, “Engineering novel restriction endonucleases: principles and applications,” Trends Biotechnol, vol. 14, no. 7, Art. no. 7, 1996, doi: 10.1016/0167-7799(96)10030-5.
    4. 14. A. Jeltsch, C. Wenz, F. Stahl, and A. Pingoud, “Linear diffusion of the restriction endonuclease EcoRV on DNA is essential for the in vivo function of the enzyme,” EMBO J, vol. 15, no. 18, Art. no. 18, 1996, [Online]. Available: http://www.ncbi.nlm.nih.gov/pubmed/8890184.
    5. 13. F. Stahl, W. Wende, A. Jeltsch, and A. Pingoud, “Introduction of asymmetry in the naturally symmetric restriction endonuclease EcoRV to investigate intersubunit communication in the homodimeric protein,” Proc Natl Acad Sci U S A, vol. 93, no. 12, Art. no. 12, 1996, doi: 10.1073/pnas.93.12.6175.
    6. 12. C. Wenz, A. Jeltsch, and A. Pingoud, “Probing the indirect readout of the restriction enzyme EcoRV. Mutational analysis of contacts to the DNA backbone,” J Biol Chem, vol. 271, no. 10, Art. no. 10, 1996, doi: 10.1074/jbc.271.10.5565.
  27. 1995

    1. 11. G. Grabowski, A. Jeltsch, H. Wolfes, G. Maass, and J. Alves, “Site-directed mutagenesis in the catalytic center of the restriction endonuclease EcoRI,” Gene, vol. 157, no. 1–2, Art. no. 1–2, 1995, doi: 10.1016/0378-1119(94)00714-4.
    2. 10. A. Jeltsch, M. Pleckaityte, U. Selent, H. Wolfes, V. Siksnys, and A. Pingoud, “Evidence for substrate-assisted catalysis in the DNA cleavage of several restriction endonucleases,” Gene, vol. 157, no. 1–2, Art. no. 1–2, 1995, doi: 10.1016/0378-1119(94)00617-2.
    3. 9. A. Jeltsch, M. Kroger, and A. Pingoud, “Evidence for an evolutionary relationship among type-II restriction endonucleases,” Gene, vol. 160, no. 1, Art. no. 1, 1995, doi: 10.1016/0378-1119(95)00181-5.
    4. 8. A. Jeltsch et al., “A dodecapeptide comprising the extended chain-alpha 4 region of the restriction endonuclease EcoRI specifically binds to the EcoRI recognition site,” J Biol Chem, vol. 270, no. 10, Art. no. 10, 1995, doi: 10.1074/jbc.270.10.5122.
    5. 7. A. Jeltsch et al., “DNA binding specificity of the EcoRV restriction endonuclease is increased by Mg2+ binding to a metal ion binding site distinct from the catalytic center of the enzyme,” Biochemistry, vol. 34, no. 18, Art. no. 18, 1995, doi: 10.1021/bi00018a028.
  28. 1994

    1. 6. A. Jeltsch, J. Alves, H. Wolfes, G. Maass, and A. Pingoud, “Pausing of the restriction endonuclease EcoRI during linear diffusion on DNA,” Biochemistry, vol. 33, no. 34, Art. no. 34, 1994, doi: 10.1021/bi00200a001.
    2. 5. C. Wenz, U. Selent, W. Wende, A. Jeltsch, H. Wolfes, and A. Pingoud, “Protein engineering of the restriction endonuclease EcoRV: replacement of an amino acid residue in the DNA binding site leads to an altered selectivity towards unmodified and modified substrates,” Biochim Biophys Acta, vol. 1219, no. 1, Art. no. 1, 1994, doi: 10.1016/0167-4781(94)90248-8.
  29. 1993

    1. 4. A. Jeltsch, J. Alves, T. Oelgeschlager, H. Wolfes, G. Maass, and A. Pingoud, “Mutational analysis of the function of Gln115 in the EcoRI restriction endonuclease, a critical amino acid for recognition of the inner thymidine residue in the sequence -GAATTC- and for coupling specific DNA binding to catalysis,” J Mol Biol, vol. 229, no. 1, Art. no. 1, 1993, doi: 10.1006/jmbi.1993.1019.
    2. 3. A. Jeltsch, A. Fritz, J. Alves, H. Wolfes, and A. Pingoud, “A fast and accurate enzyme-linked immunosorbent assay for the determination of the DNA cleavage activity of restriction endonucleases,” Anal Biochem, vol. 213, no. 2, Art. no. 2, 1993, doi: 10.1006/abio.1993.1415.
    3. 2. A. Jeltsch, J. Alves, H. Wolfes, G. Maass, and A. Pingoud, “Substrate-assisted catalysis in the cleavage of DNA by the EcoRI and EcoRV restriction enzymes,” Proc Natl Acad Sci U S A, vol. 90, no. 18, Art. no. 18, 1993, doi: 10.1073/pnas.90.18.8499.
  30. 1992

    1. 1. A. Jeltsch, J. Alves, G. Maass, and A. Pingoud, “On the catalytic mechanism of EcoRI and EcoRV. A detailed proposal based on biochemical results, structural data and molecular modelling,” FEBS Lett, vol. 304, no. 1, Art. no. 1, 1992, doi: 10.1016/0014-5793(92)80576-3.

Kontakt

Dieses Bild zeigt  Albert Jeltsch
Prof. Dr.

Albert Jeltsch

Abteilungsleiter Biochemie, geschäftsführender Institutsleiter

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