PRC1 catalytic activity is central to Polycomb system function

Journal article

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.

Authors: Blackledge, NP; Fursova, NA; Kelley, JR; Huseyin, MK; Feldmann, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Molecular Cell
• Volume: 77
• Issue: 4
• Pages: P857-874.E9
• Publication date: 2019-12-27
• Acceptance date: 2019-12-02
• DOI: 10.1016/j.molcel.2019.12.001
• EISSN: 1097-4164
• ISSN: 1097-2765
• Language: English
• Keywords: FFR