Variant PRC1 complex-dependent H2A ubiquitylation drives PRC2 recruitment and polycomb domain formation.
Bottom Line: Chromatin modifying activities inherent to polycomb repressive complexes PRC1 and PRC2 play an essential role in gene regulation, cellular differentiation, and development.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.
Affiliation: Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.Show MeSH
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Mentions: To identify polycomb sites that are dependent on KDM2B-mediated targeting for RING1B binding, RING1B ChIP-seq was carried out in the Kdm2bfl/fl and tamoxifen treated cells. Removal of the KDM2B ZF-CxxC domain resulted in a widespread reduction of RING1B chromatin binding (Figures 6A–6D). Of the 3,488 high-confidence RING1B peaks identified in ESCs, 43% showed a greater than 1.5-fold reduction in RING1B occupancy after tamoxifen treatment (Figure 6D), suggesting that a subset of RING1B-bound CpG islands is most sensitive to KDM2B loss, and other PRC1 complexes must contribute to RING1B occupancy at the remaining sites. Importantly, sites exhibiting RING1B loss also showed reduced H2AK119ub1 levels, consistent with a role for PCGF1/PRC1 in catalyzing this modification (Figure 6I).
Affiliation: Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.