期刊
MOLECULAR CELL
卷 77, 期 4, 页码 857-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2019.12.001
关键词
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资金
- Wellcome Trust [209400/Z/17/Z]
- European Research Council [681440]
- Lister Institute of Preventive Medicine
- Wellcome Trust [209400/Z/17/Z] Funding Source: Wellcome Trust
- European Research Council (ERC) [681440] Funding Source: European Research Council (ERC)
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.
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