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Updated: Oct 20, 2025

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions
Published on: June 28, 2018
Variant PCGF1-PRC1 links PRC2 recruitment with differentiation-associated transcriptional inactivation at target
Hiroki Sugishita1,2,3, Takashi Kondo1, Shinsuke Ito1
1Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Abstract:
Polycomb repressive complexes-1 and -2 (PRC1 and 2) silence developmental genes in a spatiotemporal manner during embryogenesis. How Polycomb group (PcG) proteins orchestrate down-regulation of target genes upon differentiation, however, remains elusive. Here, by differentiating embryonic stem cells into embryoid bodies, we reveal a crucial role for the PCGF1-containing variant PRC1 complex (PCGF1-PRC1) to mediate differentiation-associated down-regulation of a group of genes. Upon differentiation cues, transcription is down-regulated at these genes, in association with PCGF1-PRC1-mediated deposition of histone H2AK119 mono-ubiquitination (H2AK119ub1) and PRC2 recruitment. In the absence of PCGF1-PRC1, both H2AK119ub1 deposition and PRC2 recruitment are disrupted, leading to aberrant expression of target genes. PCGF1-PRC1 is, therefore, required for initiation and consolidation of PcG-mediated gene repression during differentiation.
Insights
The Polycomb repressive complex associated protein PCGF1-PRC1 is crucial for gene silencing during embryonic stem cell differentiation. It initiates repression by depositing histone H2AK119ub1 and recruiting PRC2, ensuring proper developmental gene regulation.
Area of Science:
- Developmental biology
- Epigenetics
- Gene regulation
Background:
- Polycomb repressive complexes (PRC1 and PRC2) are key epigenetic regulators of developmental gene expression during embryogenesis.
- The precise mechanisms by which Polycomb group (PcG) proteins control target gene downregulation during cellular differentiation are not fully understood.
Purpose of the Study:
- To elucidate the role of Polycomb group proteins in mediating gene silencing during embryonic stem cell differentiation.
- To investigate the function of the PCGF1-containing PRC1 complex (PCGF1-PRC1) in differentiation-associated gene downregulation.
Main Methods:
- Embryonic stem cells were differentiated into embryoid bodies to model early development.
- Gene expression analysis was performed to identify target genes downregulated during differentiation.
- Histone modification assays were used to detect H2AK119ub1 deposition.
- Chromatin immunoprecipitation was employed to assess PRC2 recruitment.
Main Results:
- PCGF1-PRC1 mediates the differentiation-associated downregulation of specific target genes.
- PCGF1-PRC1 activity is associated with the deposition of histone H2AK119 mono-ubiquitination (H2AK119ub1) and recruitment of PRC2.
- Loss of PCGF1-PRC1 function disrupts H2AK119ub1 deposition and PRC2 recruitment, leading to aberrant target gene expression.
Conclusions:
- PCGF1-PRC1 plays a critical role in initiating and consolidating Polycomb-mediated gene repression during cellular differentiation.
- This complex is essential for the proper spatiotemporal silencing of developmental genes required for embryogenesis.
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