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PRC1 Catalytic Activity Is Central to Polycomb System Function.

Abstract：

:The Polycomb repressive system is an essential chromatin-based regulator of gene expression. Despite being extensively studied, how the Polycomb system selects its target genes is poorly understood, and whether its histone-modifying activities are required for transcriptional repression remains controversial. Here, we directly test the requirement for PRC1 catalytic activity in Polycomb system function. To achieve this, we develop a conditional mutation system in embryonic stem cells that completely removes PRC1 catalytic activity. Using this system, we demonstrate that catalysis by PRC1 drives Polycomb chromatin domain formation and long-range chromatin interactions. Furthermore, we show that variant PRC1 complexes with DNA-binding activities occupy target sites independently of PRC1 catalytic activity, providing a putative mechanism for Polycomb target site selection. Finally, we discover that Polycomb-mediated gene repression requires PRC1 catalytic activity. Together these discoveries provide compelling evidence that PRC1 catalysis is central to Polycomb system function and gene regulation.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Blackledge NP,Fursova NA,Kelley JR,Huseyin MK,Feldmann A,Klose RJ

doi

10.1016/j.molcel.2019.12.001

subject

Has Abstract

pub_date

2020-02-20 00:00:00

pages

857-874.e9

issue

4

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(19)30892-5

journal_volume

77

pub_type

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