The Kinase NEK6 Positively Regulates LSD1 Activity and Accumulation in Local Chromatin Sub-compartments

Overview

Journal Commun Biol

Specialty Biology

Date 2024 Nov 10

PMID 39523439

Authors

Franziska Knodel

Jurgen Eirich

Sabine Pinter

Stephan A Eisler

Iris Finkemeier

Philipp Rathert

Affiliations

Soon will be listed here.

Abstract

LSD1 plays a crucial role in mammalian biology, regulated through interactions with coregulators and post-translational modifications. Here we show that the kinase NEK6 stimulates LSD1 activity in cells and observe a strong colocalization of NEK6 and LSD1 at distinct chromatin sub-compartments (CSCs). We demonstrate that LSD1 is a substrate for NEK6 phosphorylation at the N-terminal intrinsically disordered region (IDR) of LSD1, which shows phase separation behavior 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. This suggest that phase separation is crucial for the regulatory function of LSD1 and our findings highlight the role of NEK6 in modulating LSD1 activity and phase separation, expanding our understanding of LSD1 regulation and its implications in cellular processes.

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