Asymmetric histone inheritance via strand-specific incorporation and biased replication fork movement
Asymmetric histone inheritance via strand-specific incorporation and biased replication fork movement
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DOI：
10.1038/s41594-019-0269-z
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发表时间：
2019-08-01
影响因子：
16.8
通讯作者：
Chen, Xin
中科院分区：
文献类型：
--
作者：
Wooten, Matthew;Snedeker, Jonathan;Chen, Xin
许多干细胞经过不对称分裂产生自我更新的干细胞和分化的子细胞。本研究表明，与H3相似，组蛋白H4在进行不对称分裂的黑腹果蝇雄性种系干细胞中是不对称遗传的。相反，H2A和H2B都是对称遗传的。通过超分辨显微镜和染色质纤维分析以及对完整细胞核的近距离连接分析，我们发现旧的H3优先被前导链结合，而新合成的H3则在滞后链上富集。使用序列核苷类似物掺入试验，我们检测到睾丸来源的染色质和DNA纤维中单向复制叉运动的高发生率。偏向叉运动加上组蛋白结合中的链偏好可以解释在复制过程中如何建立不对称的新旧H3和H4。这些结果表明，DNA复制在多细胞生物中不对称分裂细胞的表观遗传信息中发挥了作用。
Many stem cells undergo asymmetric division to produce a self-renewing stem cell and a differentiating daughter cell. Here we show that, similarly to H3, histone H4 is inherited asymmetrically in Drosophila melanogaster male germline stem cells undergoing asymmetric division. In contrast, both H2A and H2B are inherited symmetrically. By combining super-resolution microscopy and chromatin fiber analyses with proximity ligation assays on intact nuclei, we find that old H3 is preferentially incorporated by the leading strand, whereas newly synthesized H3 is enriched on the lagging strand. Using a sequential nucleoside analog incorporation assay, we detect a high incidence of unidirectional replication fork movement in testes-derived chromatin and DNA fibers. Biased fork movement coupled with a strand preference in histone incorporation would explain how asymmetric old and new H3 and H4 are established during replication. These results suggest a role for DNA replication in patterning epigenetic information in asymmetrically dividing cells in multicellular organisms.