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Variant PCGF1-PRC1 links PRC2 recruitment with differentiation-associated transcriptional inactivation at target genes

Author

Listed:
  • Hiroki Sugishita

    (RIKEN Center for Integrative Medical Sciences
    Chiba University
    The University of Tokyo)

  • Takashi Kondo

    (RIKEN Center for Integrative Medical Sciences)

  • Shinsuke Ito

    (RIKEN Center for Integrative Medical Sciences)

  • Manabu Nakayama

    (Kazusa DNA Research Institute)

  • Nayuta Yakushiji-Kaminatsui

    (RIKEN Center for Integrative Medical Sciences)

  • Eiryo Kawakami

    (Chiba University
    RIKEN Medical Sciences Innovation Hub Program)

  • Yoko Koseki

    (RIKEN Center for Integrative Medical Sciences
    Chiba University)

  • Yasuhide Ohinata

    (RIKEN Center for Integrative Medical Sciences
    Chiba University)

  • Jafar Sharif

    (RIKEN Center for Integrative Medical Sciences)

  • Mio Harachi

    (RIKEN Center for Integrative Medical Sciences)

  • Neil P. Blackledge

    (University of Oxford)

  • Robert J. Klose

    (University of Oxford)

  • Haruhiko Koseki

    (RIKEN Center for Integrative Medical Sciences
    Chiba University)

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.

Suggested Citation

  • Hiroki Sugishita & Takashi Kondo & Shinsuke Ito & Manabu Nakayama & Nayuta Yakushiji-Kaminatsui & Eiryo Kawakami & Yoko Koseki & Yasuhide Ohinata & Jafar Sharif & Mio Harachi & Neil P. Blackledge & Ro, 2021. "Variant PCGF1-PRC1 links PRC2 recruitment with differentiation-associated transcriptional inactivation at target genes," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24894-z
    DOI: 10.1038/s41467-021-24894-z
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    Cited by:

    1. Junichiro Takano & Shinsuke Ito & Yixing Dong & Jafar Sharif & Yaeko Nakajima-Takagi & Taichi Umeyama & Yong-Woon Han & Kyoichi Isono & Takashi Kondo & Yusuke Iizuka & Tomohiro Miyai & Yoko Koseki & M, 2022. "PCGF1-PRC1 links chromatin repression with DNA replication during hematopoietic cell lineage commitment," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Bo Zhang & Chen Zhao & Wenchen Shen & Wei Li & Yue Zheng & Xiangfei Kong & Junbao Wang & Xudong Wu & Tao Zeng & Ying Liu & Yan Zhou, 2023. "KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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