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

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, Mika Ikegaya, Mizuki Sakihara, Manabu Nakayama, Osamu Ohara, Yoshinori Hasegawa, Kosuke Hashimoto, Erik Arner, Robert J. Klose, Atsushi Iwama, Haruhiko Koseki () and Tomokatsu Ikawa ()
Additional contact information
Junichiro Takano: RIKEN Center for Integrative Medical Sciences (RIKEN-IMS)
Shinsuke Ito: RIKEN Center for Integrative Medical Sciences
Yixing Dong: RIKEN Center for Integrative Medical Sciences
Jafar Sharif: RIKEN Center for Integrative Medical Sciences
Yaeko Nakajima-Takagi: The Institute of Medical Science, University of Tokyo
Taichi Umeyama: Laboratory for Microbiome Sciences, RIKEN-IMS
Yong-Woon Han: Laboratory for Integrative Genomics, RIKEN-IMS
Kyoichi Isono: RIKEN Center for Integrative Medical Sciences
Takashi Kondo: RIKEN Center for Integrative Medical Sciences
Yusuke Iizuka: RIKEN Center for Integrative Medical Sciences
Tomohiro Miyai: RIKEN Center for Integrative Medical Sciences
Yoko Koseki: RIKEN Center for Integrative Medical Sciences
Mika Ikegaya: RIKEN Center for Integrative Medical Sciences (RIKEN-IMS)
Mizuki Sakihara: Tokyo University of Science, Noda
Manabu Nakayama: Kazusa DNA Research Institute
Osamu Ohara: Kazusa DNA Research Institute
Yoshinori Hasegawa: Kazusa DNA Research Institute
Kosuke Hashimoto: Institute for Protein Research
Erik Arner: Laboratory for Applied Regulatory Genomics Network Analysis, RIKEN-IMS
Robert J. Klose: University of Oxford
Atsushi Iwama: The Institute of Medical Science, University of Tokyo
Haruhiko Koseki: RIKEN Center for Integrative Medical Sciences
Tomokatsu Ikawa: RIKEN Center for Integrative Medical Sciences (RIKEN-IMS)

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34856-8

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