Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation
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Volume
157
Pagination
1445 - 1459
Publisher
DOI
10.1016/j.cell.2014.05.004
Journal
CELL
Issue
ISSN
0092-8674
Metadata
Show full item recordAbstract
Chromatin modifying activities inherent to polycomb
repressive complexes PRC1 and PRC2 play an
essential role in gene regulation, cellular differentiation, and development. However, the mechanisms
by which these complexes recognize their target
sites and function together to form repressive chromatin domains remain poorly understood. Recruitment of PRC1 to target sites has been proposed to
occur through a hierarchical process, dependent
on prior nucleation of PRC2 and placement of
H3K27me3. Here, using a de novo targeting assay
in mouse embryonic stem cells we unexpectedly
discover that PRC1-dependent H2AK119ub1 leads
to recruitment of PRC2 and H3K27me3 to effectively
initiate a polycomb domain. This activity is restricted
to variant PRC1 complexes, and genetic ablation
experiments reveal that targeting of the variant
PCGF1/PRC1 complex by KDM2B to CpG islands is
required for normal polycomb domain formation
and mouse development. These observations provide a surprising PRC1-dependent logic for PRC2
occupancy at target sites in vivo.
Authors
Blackledge, NP; Farcas, AM; Kondo, T; King, HW; McGouran, JF; Hanssen, LLP; Ito, S; Cooper, S; Kondo, K; Koseki, YCollections
- Centre for Immunobiology [1121]
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