PCGF1-PRC1 在造血细胞谱系定型过程中将染色质抑制与 DNA 复制联系起来,Nature Communications

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PCGF1-PRC1 在造血细胞谱系定型过程中将染色质抑制与 DNA 复制联系起来
Nature Communications ( IF 14.7 ) Pub Date : 2022-11-28 , 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 _{2,

3} , Tomokatsu Ikawa _{1,

8}

Affiliation

Laboratory for Immune Regeneration, RIKEN Center for Integrative Medical Sciences (RIKEN-IMS), Yokohama, Kanagawa, Japan.
Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
Department of Cellular and Molecular Medicine, Graduate School of Medical and Pharmaceutical Sciences, Chiba University, Chiba, Japan.
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.
Laboratory for Microbiome Sciences, RIKEN-IMS, Yokohama, Kanagawa, Japan.
Laboratory for Integrative Genomics, RIKEN-IMS, Yokohama, Kanagawa, Japan.
Laboratory Animal Center, Wakayama Medical University, Wakayama, Japan.
Division of Immunology and Allergy, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Chromosome Engineering Team, Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan.
Laboratory of Computational Biology, Institute for Protein Research, Osaka University, Osaka, Japan.
Laboratory for Transcriptome Technology, RIKEN-IMS, Yokohama, Kanagawa, Japan.
Laboratory for Applied Regulatory Genomics Network Analysis, RIKEN-IMS, Yokohama, Kanagawa, Japan.
Department of Biochemistry, University of Oxford, Oxford, UK.

多梳组蛋白 (PcG)、多梳抑制复合物 1 和 2（PRC1 和 2）在发育过程中抑制谱系不当基因以维持适当的细胞特性。人们已经认识到 PRC1 位于复制叉处，但是，PRC1 在 DNA 复制过程中的确切功能尚不清楚。在这里，我们发现含有 PCGF1 (PCGF1-PRC1) 的变体 PRC1 可防止活化剂和染色质重塑因子在新生 DNA 上超载，从而介导核小体的正确沉积并纠正造血干细胞和祖细胞 (HSPC) 中的下游染色质配置。PCGF1-PRC1 的这种功能反过来促进了 PRC2 介导的对靶基因（如Hmga2 ）的抑制并限制过早的骨髓分化。因此，PCGF1-PRC1 通过将复制叉处的正确核小体配置与 PcG 介导的基因沉默联系起来以确保终生造血来维持 HSPC 的分化潜能。

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更新日期：2022-11-28

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