The kinase NEK6 positively regulates LSD1 activity and accumulation in local chromatin sub-compartments (CSCs)

ABSTRACT: LSD1 is involved in multiple essential roles in mammalian biology and various modes of LSD1 regulation are described ranging from interaction with specific coregulators to distinct post translational modifications. Here we show that NEK6 positively influences LSD1 activity and we observe a strong colocalization of NEK6 and LSD1 at distinct chromatin sub-compartments (CSCs). We further demonstrate that LSD1 is a substrate for NEK6-mediated phosphorylation at the highly conserved, but intrinsic disordered region (IDR) of LSD1, which shows phase separation behaviour in-vitro and in cells. Furthermore, the IDR of LSD1 is important for LSD1 activity and functions to co-compartmentalize histone tails. Our data suggest that LSD1 and NEK6 form distinct CSCs in part through the formation of phase-separated condensates. The subsequent phosphorylation of LSD1 by NEK6 within these CSCs aids to concentrate more LSD1 leading to co-compartmentalisation of histone substrates, which is imperative for dynamic and robust control of transcription.

ORGANISM(S): Escherichia Coli

SUBMITTER: Iris Finkemeier 

PROVIDER: PXD049227 | JPOST Repository | Sun Oct 27 00:00:00 BST 2024

REPOSITORIES: jPOST