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Variant PCGF1-PRC1 links PRC2 recruitment with induced transcriptional inactivation at target genes [RNA-seq]

ABSTRACT: Polycomb repressive complexes-1 and -2 (PRC1 and 2), silence developmental genes in spatiotemporally regulated manner during metazoan embryogenesis. How PcG proteins contribute to down-regulation of target genes upon differentiation, however, remains elusive. Here, by differentiating embryonic stem cells into embryoid bodies, we reveal a crucial role of a PCGF1 (Polycomb group RING finger protein 1)-containing variant PRC1 complex (PCGF1-PRC1) to facilitate induced down-regulation of a group of genes. Binding of PCGF1-PRC1 results in down-regulation of transcriptional activity, followed by Histone H2AK119 mono-ubiquitination (H2AK119ub1) and subsequent recruitment of PRC2, to initiate PcG-repressive domain formation. Based on these findings, we propose that PCGF1-PRC1 mediates establishment of PcG-repressive domains at target genes during differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE141487 | GEO | 2021/05/31

REPOSITORIES: GEO

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Variant PCGF1-PRC1 links PRC2 recruitment with induced transcriptional inactivation at target genes [CUT&Tag]

Project description:Polycomb repressive complexes-1 and -2 (PRC1 and 2), silence developmental genes in spatiotemporally regulated manner during metazoan embryogenesis. How PcG proteins contribute to down-regulation of target genes upon differentiation, however, remains elusive. Here, by differentiating embryonic stem cells into embryoid bodies, we reveal a crucial role of a PCGF1 (Polycomb group RING finger protein 1)-containing variant PRC1 complex (PCGF1-PRC1) to facilitate induced down-regulation of a group of genes. Binding of PCGF1-PRC1 results in down-regulation of transcriptional activity, followed by Histone H2AK119 mono-ubiquitination (H2AK119ub1) and subsequent recruitment of PRC2, to initiate PcG-repressive domain formation. Based on these findings, we propose that PCGF1-PRC1 mediates establishment of PcG-repressive domains at target genes during differentiation.

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Variant PCGF1-PRC1 links PRC2 recruitment with induced transcriptional inactivation at target genes [ChIP-seq]

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Project description:Polycomb group (PcG) proteins are critical chromatin regulators for cell fate control. The mono-ubiquitylation on histone H2AK119 (H2AK119ub1) is one of the well-recognized mechanisms for Polycomb Repressive Complex 1 (PRC1)-mediated transcription repression. However, the specific H2AK119 deubiquitylation complex composed by ASX-like proteins (ASXLs) and BAP1 has also been genetically characterized as a Polycomb Repressive complex (PR-DUB). Here we try to provide a rationale for these counterintuitive findings. Through re-examining the genomic distribution of H2AK119ub1, we find that H2AK119ub1 is non-negligibly distributed at non-promoter regions and associated with PRC1 sampling. Upon deletion of Asxl2 in mouse embryonic stem cells (ESCs), H2AK119ub1 is pervasively gained, especially at non-promoter regions, which is associated with increased RING1B occupancy. Meanwhile RING1B is significantly lost from a subset of the target promoters and thereby results in minor derepression in Asxl2-null ESCs. However notably, Asxl2 loss causes aberrant lineage differetiation, similar to PcG mutants. Therefore, our data reconcile seemingly paradoxical roles of PR-DUB on transcription repression and highlight the importance of a balanced H2AK119ub1 dynamics in developmental regulation.

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