組蛋白H1通過染色質壓實促進DNA復制過程中H3K27me3的恢復

2023年7月10日，中國科學院生物物理研究所，中國科學院生物大分子**研究中心，生物大分子國家實驗室，中國科學院大學，

中國科學院生物物理研究所RNA生物學重點實驗室，首都醫科大學基礎醫學院免疫學系，腫瘤侵襲與轉移北京市重點實驗室，湖北省細胞穩態重點實驗室，生命科學學院，

太康生命醫學中心，武漢大學理學院，（National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101 Beijing, China.

University of Chinese Academy of Sciences, 100049 Beijing, China.

Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy ofScience, 100101 Beijing, China.

Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory for Tumor Invasion and Metastasis,Capital Medical University, 100069 Beijing, China.

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical

Sciences, Wuhan University, 430072 Wuhan, China.） Jicheng Zhao & Guohong Li 研究團隊在《》發表論文，標題為：“Histone H1 facilitates restoration of H3K27me3 during DNA replication by chromatin compaction ”“組蛋白H1通過染色質壓實促進DNA復制過程中H3K27me3的恢復”

Abstract

During cell renewal, epigenetic information needs to be precisely restored to maintain cell identity and genome integrity following DNA replication.   The histone mark H3K27me3 is essential for the formation of facultative heterochromatin and the repression of developmental genes in embryonic stem cells.   However, how the restoration of H3K27me3 is precisely achieved following DNA replication is still poorly understood.   Here we employ ChOR-seq (Chromatin Occupancy after Replication) to monitor the dynamic re-establishment of H3K27me3 on nascent DNA during DNA replication.   We find that the restoration rate of H3K27me3 is highly correlated with dense chromatin states.   In addition, we reveal that the linker histone H1 facilitates the rapid post-replication restoration of H3K27me3 on repressed genes and the restoration rate of H3K27me3 on nascent DNA is greatly compromised after partial depletion of H1.   Finally, our in vitro biochemical experiments demonstrate that H1 facilitates the propagation of H3K27me3 by PRC2 through compacting chromatin.   Collectively, our results indicate that H1-mediated chromatin compaction facilitates the propagation and restoration of H3K27me3 after DNA replication.

摘要

在細胞更新過程中，表觀遺傳信息需要精確地恢復，以維持DNA復制后的細胞身份和基因組完整性。組蛋白標記H3K27me3對胚胎干細胞兼性異染色質的形成和發育基因的抑制至關重要。然而，H3K27me3是如何在DNA復制后精確地恢復的，我們仍然知之甚少。在這里，我們使用ChOR-seq(復制后染色質占用)來監測DNA復制過程中H3K27me3在新生DNA上的動態重建。我們發現H3K27me3的恢復速率與致密染色質狀態高度相關。此外，我們發現連接蛋白H1促進H3K27me3在抑制基因上的復制后快速恢復，并且在H1部分耗盡后，H3K27me3在新生DNA上的恢復速率大大降低。最后，我們的體外生化實驗表明，H1通過壓實染色質促進PRC2對H3K27me3的增殖。總之，我們的研究結果表明，h1介導的染色質壓實有助于DNA復制后H3K27me3的繁殖和恢復。

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