美国纽约大学朗格尼医学中心Danny Reinberg研究组发现，DNA复制过程中活跃和受抑制的染色质结构域表现出不同的核小体分离特征。该项研究成果发表在2019年10月31日出版的《细胞》杂志上。

他们设计了一种可诱导的，邻近依赖性的标记系统，该系统可以不可逆转地在小鼠胚胎干细胞中所需基因座上标记复制依赖性的含有H3.1和H3.2组蛋白的核小体，以便追踪它们在DNA复制后的命运。令人惊讶的是，通过亲本核小体的局部重分布可以保留被抑制的染色质结构域。相反，修饰活跃的染色质结构域的核小体不表现出这种特性。

值得注意的是，改变细胞命运会导致亲本核小体位置遗传的调整，从而反映出染色质结构的相应变化。这些研究结果指出帮助亲本核小体分离以保持细胞特性的重要机制。

据了解，染色质结构域及其相关结构必须通过细胞分裂保持遗传保真性，并维持细胞特性。然而，在活细胞中，获取保留染色质结构域遗传的定位策略，特别是在DNA复制过程中亲本染色质转移以及已有核小体及其相关的翻译后修饰，是一项挑战。

附：英文原文

Title: Active and Repressed Chromatin Domains Exhibit Distinct Nucleosome Segregation during DNA Replication

Author: Thelma M. Escobar, Ozgur Oksuz, Ricardo Saldaa-Meyer, Nicolas Descostes, Roberto Bonasio, Danny Reinberg

Issue&Volume: 2019/10/31

Abstract: Chromatin domains and their associated structures must be faithfully inherited through cellular division to maintain cellular identity. However, accessing the localized strategies preserving chromatin domain inheritance, specifically the transfer of parental, pre-existing nucleosomes with their associated post-translational modifications (PTMs) during DNA replication, is challenging in living cells. We devised an inducible, proximity-dependent labeling system to irreversibly mark replication-dependent H3.1 and H3.2 histone-containing nucleosomes at desired loci in mouse embryonic stem cells so that their fate after DNA replication could be followed. Strikingly, repressed chromatin domains are preserved through local re-deposition of parental nucleosomes. In contrast, nucleosomes decorating active chromatin domains do not exhibit such preservation. Notably, altering cell fate leads to an adjustment of the positional inheritance of parental nucleosomes that reflects the corresponding changes in chromatin structure. These findings point to important mechanisms that contribute to parental nucleosome segregation to preserve cellular identity.

DOI: 10.1016/j.cell.2019.10.009

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31125-0