New publication in "Communications Biology"

In this publication Franziska Knodel, PhD student in the group of Philipp Rathert, characterized the kinase NEK6 as a novel coregulator of LSD1. Franziska showed that the NEK6 stimulates LSD1 activity in cells and observed a strong colocalization of NEK6 and LSD1 at distinct chromatin sub-compartments (CSCs). In cooperation with researchers from the University Münster she demonstrated that LSD1 is a substrate for NEK6 phosphorylation at the N-terminal intrinsically disordered region (IDR) of LSD1, which shows phase separation behaviour in vitro and in cells. The LSD1-IDR is important for LSD1 activity and functions to co-compartmentalize NEK6, histone peptides and DNA. The subsequent phosphorylation of LSD1 by NEK6 supports the concentration of LSD1 at these distinct CSCs, which is imperative for dynamic control of transcription. LSD1 plays crucial roles in mammalian biology, regulated through interactions with coregulators and post-translational modifications. The new data suggest that phase separation is crucial for the regulatory function of LSD1 and is regulated by the coregulator NEK6, which modulates LSD1 activity and phase separation. This expanding the molecular understanding of LSD1 regulation and its implications in cellular processes.