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.

Here the authors show that a Polycomb Repressive Complex 1 (PRC1) containing PCGF1 prevents excessive loading of transcriptional activators and chromatin remodelers on nascent DNA, allowing proper deposition of nucleosomes immediately after the passage of the DNA replication fork to optimize downstream chromatin configurations in hematopoietic stem and progenitor cells (HSPCs).

Details

Title
PCGF1-PRC1 links chromatin repression with DNA replication during hematopoietic cell lineage commitment
Author
Takano, Junichiro 1 ; Ito, Shinsuke 2 ; Dong, Yixing 2 ; Sharif, Jafar 2   VIAFID ORCID Logo  ; Nakajima-Takagi, Yaeko 3 ; Umeyama, Taichi 4 ; Han, Yong-Woon 5   VIAFID ORCID Logo  ; Isono, Kyoichi 6 ; Kondo, Takashi 2   VIAFID ORCID Logo  ; Iizuka, Yusuke 2 ; Miyai, Tomohiro 2   VIAFID ORCID Logo  ; Koseki, Yoko 2 ; Ikegaya, Mika 7 ; Sakihara, Mizuki 8 ; Nakayama, Manabu 9 ; Ohara, Osamu 9 ; Hasegawa, Yoshinori 9 ; Hashimoto, Kosuke 10 ; Arner, Erik 11   VIAFID ORCID Logo  ; Klose, Robert J. 12   VIAFID ORCID Logo  ; Iwama, Atsushi 3 ; Koseki, Haruhiko 13   VIAFID ORCID Logo  ; Ikawa, Tomokatsu 14 

1  RIKEN Center for Integrative Medical Sciences (RIKEN-IMS), Laboratory for Immune Regeneration, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267); RIKEN Center for Integrative Medical Sciences, Laboratory for Developmental Genetics, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267); Graduate School of Medical and Pharmaceutical Sciences, Chiba University, Department of Cellular and Molecular Medicine, Chiba, Japan (GRID:grid.136304.3) (ISNI:0000 0004 0370 1101) 
2  RIKEN Center for Integrative Medical Sciences, Laboratory for Developmental Genetics, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267) 
3  The Institute of Medical Science, University of Tokyo, Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
4  Laboratory for Microbiome Sciences, RIKEN-IMS, Yokohama, Japan (GRID:grid.7597.c) (ISNI:0000000094465255) 
5  Laboratory for Integrative Genomics, RIKEN-IMS, Yokohama, Japan (GRID:grid.7597.c) (ISNI:0000000094465255) 
6  RIKEN Center for Integrative Medical Sciences, Laboratory for Developmental Genetics, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267); Wakayama Medical University, Laboratory Animal Center, Wakayama, Japan (GRID:grid.412857.d) (ISNI:0000 0004 1763 1087) 
7  RIKEN Center for Integrative Medical Sciences (RIKEN-IMS), Laboratory for Immune Regeneration, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267); RIKEN Center for Integrative Medical Sciences, Laboratory for Developmental Genetics, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267) 
8  Tokyo University of Science, Noda, Division of Immunology and Allergy, Research Institute for Biomedical Sciences, Chiba, Japan (GRID:grid.143643.7) (ISNI:0000 0001 0660 6861) 
9  Kazusa DNA Research Institute, Chromosome Engineering Team, Department of Technology Development, Kisarazu, Japan (GRID:grid.410858.0) (ISNI:0000 0000 9824 2470) 
10  Institute for Protein Research, Laboratory of Computational Biology, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971); Laboratory for Transcriptome Technology, RIKEN-IMS, Yokohama, Japan (GRID:grid.7597.c) (ISNI:0000000094465255) 
11  Laboratory for Applied Regulatory Genomics Network Analysis, RIKEN-IMS, Yokohama, Japan (GRID:grid.7597.c) (ISNI:0000000094465255) 
12  University of Oxford, Department of Biochemistry, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
13  RIKEN Center for Integrative Medical Sciences, Laboratory for Developmental Genetics, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267); Graduate School of Medical and Pharmaceutical Sciences, Chiba University, Department of Cellular and Molecular Medicine, Chiba, Japan (GRID:grid.136304.3) (ISNI:0000 0004 0370 1101) 
14  RIKEN Center for Integrative Medical Sciences (RIKEN-IMS), Laboratory for Immune Regeneration, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267); Tokyo University of Science, Noda, Division of Immunology and Allergy, Research Institute for Biomedical Sciences, Chiba, Japan (GRID:grid.143643.7) (ISNI:0000 0001 0660 6861) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-022-34856-8
ProQuest document ID
2740755060
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.