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组蛋白 H1 通过染色质紧缩促进 DNA 复制过程中 H3K27me3 的恢复。

Histone H1 facilitates restoration of H3K27me3 during DNA replication by chromatin compaction.

机构信息

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.

出版信息

Nat Commun. 2023 Jul 10;14(1):4081. doi: 10.1038/s41467-023-39846-y.

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

在细胞更新过程中,需要精确地恢复表观遗传信息,以在 DNA 复制后维持细胞身份和基因组完整性。组蛋白标记 H3K27me3 对于胚胎干细胞中形成兼性异染色质和抑制发育基因至关重要。然而,在 DNA 复制后,H3K27me3 的恢复是如何精确实现的,目前仍知之甚少。在这里,我们采用 ChOR-seq(复制后染色质占有率)来监测 DNA 复制过程中新生 DNA 上 H3K27me3 的动态重建。我们发现,H3K27me3 的恢复速率与致密染色质状态高度相关。此外,我们揭示了连接组蛋白 H1 有助于 PRC2 在抑制基因上快速进行复制后 H3K27me3 的恢复,并且在 H1 部分耗尽后,新生 DNA 上 H3K27me3 的恢复速率大大降低。最后,我们的体外生化实验表明,H1 通过压缩染色质促进 PRC2 传播 H3K27me3。总之,我们的结果表明,H1 介导的染色质紧缩有助于 DNA 复制后 H3K27me3 的传播和恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b632/10333366/04f0c36d1cc1/41467_2023_39846_Fig1_HTML.jpg

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