Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation
Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation
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DOI：
10.1038/s41588-023-01477-w
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发表时间：
2023-09
期刊：
影响因子：
30.8
通讯作者：
Qing Wen;Jiaqi Zhou;Congcong Tian;Xinran Li;G. Song;Yuan Gao;Yaping Sun;Chiyuan Ma;Sitong Yao;Xiaoyan Liang;Xing Kang;Nan Wang;Yuan Yao;Hongbao Wang;Xiaohuan Liang;Jialin Tang;S. Offer;Xiaohua Lei;Chuanhe Yu;Xiangyu Liu;Zichuan Liu;Zhiquan Wang;Haiyun Gan
中科院分区：
文献类型：
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作者：
Qing Wen;Jiaqi Zhou;Congcong Tian;Xinran Li;G. Song;Yuan Gao;Yaping Sun;Chiyuan Ma;Sitong Yao;Xiaoyan Liang;Xing Kang;Nan Wang;Yuan Yao;Hongbao Wang;Xiaohuan Liang;Jialin Tang;S. Offer;Xiaohua Lei;Chuanhe Yu;Xiangyu Liu;Zichuan Liu;Zhiquan Wang;Haiyun Gan
亲本组蛋白是翻译后修饰的载体，在依赖于DNA解旋酶Mcm 2亚基和DNA聚合酶Pole 3亚基的过程中均匀地沉积在姐妹染色单体的复制DNA上。亲本组蛋白繁殖的生物学意义仍不清楚。在这里，我们发现Mcm 2突变或Pole 3缺失的小鼠胚胎干细胞（ESCs）显示异常的组蛋白景观和受损的神经分化。Mcm 2组蛋白结合结构域的突变导致植入前发育和胚胎致死的缺陷。偏性亲本组蛋白转移的ESC表现出增加的表观遗传异质性，在调节分化基因的基因组位点显示改变的组蛋白变体H3.3和H3 K27 me 3模式。我们的研究结果表明H3.3的滞后链模式导致H3 K27 me 3在Mcm 2 -2A ESCs中的重新分布。我们证明，对称的亲本组蛋白沉积到姐妹染色单体有助于细胞分化和发育。
Parental histones, the carriers of posttranslational modifications, are deposited evenly onto the replicating DNA of sister chromatids in a process dependent on the Mcm2 subunit of DNA helicase and the Pole3 subunit of leading-strand DNA polymerase. The biological significance of parental histone propagation remains unclear. Here we show that Mcm2-mutated or Pole3-deleted mouse embryonic stem cells (ESCs) display aberrant histone landscapes and impaired neural differentiation. Mutation of the Mcm2 histone-binding domain causes defects in pre-implantation development and embryonic lethality. ESCs with biased parental histone transfer exhibit increased epigenetic heterogeneity, showing altered histone variant H3.3 and H3K27me3 patterning at genomic sites regulating differentiation genes. Our results indicate that the lagging strand pattern of H3.3 leads to the redistribution of H3K27me3 in Mcm2-2A ESCs. We demonstrate that symmetric parental histone deposition to sister chromatids contributes to cellular differentiation and development.