Institute for Cancer Genetics, Columbia University Irving Medical Center, New York, NY, USA.
Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
Nat Commun. 2022 May 6;13(1):2514. doi: 10.1038/s41467-022-30298-4.
Newly synthesized H3.1 and H3.3 histones are assembled into nucleosomes by different histone chaperones in replication-coupled and replication-independent pathways, respectively. However, it is not clear how parental H3.3 molecules are transferred following DNA replication, especially when compared to H3.1. Here, by monitoring parental H3.1- and H3.3-SNAP signals, we show that parental H3.3, like H3.1, are stably transferred into daughter cells. Moreover, Mcm2-Pola1 and Pole3-Pole4, two pathways involved in parental histone transfer based upon the analysis of modifications on parental histones, participate in the transfer of both H3.1 and H3.3 following DNA replication. Lastly, we found that Mcm2, Pole3 and Pole4 mutants defective in parental histone transfer show defects in chromosome segregation. These results indicate that in contrast to deposition of newly synthesized H3.1 and H3.3, transfer of parental H3.1 and H3.3 is mediated by these shared mechanisms, which contributes to epigenetic memory of gene expression and maintenance of genome stability.
新合成的 H3.1 和 H3.3 组蛋白分别通过复制偶联和非复制途径中的不同组蛋白伴侣组装到核小体中。然而，目前尚不清楚在 DNA 复制后如何转移亲本 H3.3 分子，特别是与 H3.1 相比。在这里，通过监测亲本 H3.1 和 H3.3-SNAP 信号，我们表明亲本 H3.3 与 H3.1 一样，可稳定地转移到子细胞中。此外，Mcm2-Pola1 和 Pole3-Pole4 两条途径基于亲本组蛋白修饰的分析，参与 DNA 复制后 H3.1 和 H3.3 的转移。最后，我们发现，在亲本组蛋白转移中缺陷的 Mcm2、Pole3 和 Pole4 突变体在染色体分离中表现出缺陷。这些结果表明，与新合成的 H3.1 和 H3.3 的沉积相反，亲本 H3.1 和 H3.3 的转移是由这些共享机制介导的，这有助于基因表达的表观遗传记忆和基因组稳定性的维持。
