2. Academic Validation
  3. PCGF1-PRC1 links chromatin repression with DNA replication during hematopoietic cell lineage commitment

PCGF1-PRC1 links chromatin repression with DNA replication during hematopoietic cell lineage commitment

  • Nat Commun. 2022 Nov 28;13(1):7159. doi: 10.1038/s41467-022-34856-8.
Junichiro Takano 1 2 3,  Shinsuke Ito 2,  Yixing Dong 2,  Jafar Sharif 2,  Yaeko Nakajima-Takagi 4,  Taichi Umeyama 5,  Yong-Woon Han 6,  Kyoichi Isono 2 7,  Takashi Kondo 2,  Yusuke Iizuka 2,  Tomohiro Miyai 2,  Yoko Koseki 2,  Mika Ikegaya 1 2,  Mizuki Sakihara 8,  Manabu Nakayama 9,  Osamu Ohara 9,  Yoshinori Hasegawa 9,  Kosuke Hashimoto 10 11,  Erik Arner 12,  Robert J Klose 13,  Atsushi Iwama 4,  Haruhiko Koseki 14 15,  Tomokatsu Ikawa 16 17
Affiliations

Affiliations

  • 1 Laboratory for Immune Regeneration, RIKEN Center for Integrative Medical Sciences (RIKEN-IMS), Yokohama, Kanagawa, Japan.
  • 2 Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
  • 3 Department of Cellular and Molecular Medicine, Graduate School of Medical and Pharmaceutical Sciences, Chiba University, Chiba, Japan.
  • 4 Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • 5 Laboratory for Microbiome Sciences, RIKEN-IMS, Yokohama, Kanagawa, Japan.
  • 6 Laboratory for Integrative Genomics, RIKEN-IMS, Yokohama, Kanagawa, Japan.
  • 7 Laboratory Animal Center, Wakayama Medical University, Wakayama, Japan.
  • 8 Division of Immunology and Allergy, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
  • 9 Chromosome Engineering Team, Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan.
  • 10 Laboratory of Computational Biology, Institute for Protein Research, Osaka University, Osaka, Japan.
  • 11 Laboratory for Transcriptome Technology, RIKEN-IMS, Yokohama, Kanagawa, Japan.
  • 12 Laboratory for Applied Regulatory Genomics Network Analysis, RIKEN-IMS, Yokohama, Kanagawa, Japan.
  • 13 Department of Biochemistry, University of Oxford, Oxford, UK.
  • 14 Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan. haruhiko.koseki@riken.jp.
  • 15 Department of Cellular and Molecular Medicine, Graduate School of Medical and Pharmaceutical Sciences, Chiba University, Chiba, Japan. haruhiko.koseki@riken.jp.
  • 16 Laboratory for Immune Regeneration, RIKEN Center for Integrative Medical Sciences (RIKEN-IMS), Yokohama, Kanagawa, Japan. ikawa@rs.tus.ac.jp.
  • 17 Division of Immunology and Allergy, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan. ikawa@rs.tus.ac.jp.
PMID: 36443290 DOI: 10.1038/s41467-022-34856-8
Abstract

Polycomb group proteins (PcG), polycomb repressive complexes 1 and 2 (PRC1 and 2), repress lineage inappropriate genes during development to maintain proper cellular identities. It has been recognized that PRC1 localizes at the replication fork, however, the precise functions of PRC1 during DNA replication are elusive. Here, we reveal that a variant PRC1 containing PCGF1 (PCGF1-PRC1) prevents overloading of activators and chromatin remodeling factors on nascent DNA and thereby mediates proper deposition of nucleosomes and correct downstream chromatin configurations in hematopoietic stem and progenitor cells (HSPCs). This function of PCGF1-PRC1 in turn facilitates PRC2-mediated repression of target genes such as Hmga2 and restricts premature myeloid differentiation. PCGF1-PRC1, therefore, maintains the differentiation potential of HSPCs by linking proper nucleosome configuration at the replication fork with PcG-mediated gene silencing to ensure life-long hematopoiesis.

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