New publication in "J. Mol. Biol."

December 13, 2012 / Albert Jeltsch

Targeted DNA methylation and gene silencing

DNA Methylation is an important mechanism of epigenetic gene regulation. In this project, we plan to fuse DNA methyltransferases to Zinc finger proteins that target the chimeric enzyme to promoters of oncogenes. In a cooperation with the group of Prof. Dr. M.G. Rots (Groningen), we fused DNA methyltransferases to zinc finger proteins, which direct these chimeric enzymes to promotors of oncogenes in tumor cells. Using protein design, we also generated a variant of a human DNA methyltransferase, which has increased activity and is optimized for the application of targeted DNA methlyation. We showed that this approach allows to introduce DNA methylation specifically into the human genome and that this leads to a stable and specific inhibition of gene expression of target genes. This work documents for the first time the applicability of this innovative approach to gene regulation, which has numerous potential applications in basic and medical research.

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