The conserved histone variant H2A.Z illuminates meiotic recombination initiation.
The conserved histone variant H2A.Z illuminates meiotic recombination initiation.
复制标题
保守的组蛋白变体 H2A.Z 阐明了减数分裂重组的起始。
DOI：
10.1007/s00294-018-0825-9
复制
发表时间：
2018
期刊：
影响因子：
2.5
通讯作者：
Yamada T.
中科院分区：
文献类型：
--
作者：
Yamada S;Kugou K;Ding DQ;Fujita Y;Hiraoka Y;Murakami H;Ohta K;Yamada T.
减数分裂重组确保了染色体的可靠分离，并赋予配子遗传多样性，因此，它不仅是有性生殖的关键DNA模板反应，也是进化的关键。这种重组是由程序性DNA双链断裂（DSB）启动的，DSB主要形成于重组热点。由于减数分裂DSB的形成需要多种蛋白质，因此它受染色质结构的调节。特别地，DSB发生在称为“轴-环”的高级染色质结构中，其中许多环从蛋白质轴突出。以前的研究表明，这种结构的组装依赖于染色质结合的粘附素，这反过来又招募蛋白质参与DSB的形成。然而，染色质在减数分裂DSB形成中的作用还没有完全确定。这篇综述文章总结了我们最近的报告显示，保守的组蛋白H2 A变体H2A.Z促进分裂酵母减数分裂DSB的形成。通过一系列的实验，我们发现，在H2 A. Z缺失突变体中，参与DSB形成的多种蛋白，而不是粘附素亚基，与染色质的相关性较低。引人注目的是，在不存在H2A.Z的情况下，细胞核更致密。这些观察使我们提出，裂殖酵母H2A.Z促进减数分裂DSB形成部分通过调节染色体结构，以增强DSB相关蛋白和粘着蛋白负载的染色质之间的相互作用。此外，我们的研究结果的生物学意义进行了讨论，其相关性DSB形成在其他物种以及其他DNA相关的事件也提供。
Meiotic recombination ensures faithful chromosome segregation and confers genetic diversity to gametes, and thus, is a key DNA-templated reaction not only for sexual reproduction, but also evolution. This recombination is initiated by programmed DNA double strand breaks (DSBs), which are mainly formed at recombination hotspots. As meiotic DSB formation requires multiple proteins, it is regulated by chromatin structure. In particular, DSB occurs in a higher-order chromatin architecture termed “axis-loop”, in which many loops protrude from proteinaceous axis. Previous studies have suggested that assembly of this structure is dependent on chromatin binding of cohesin, which in turn recruits proteins implicated in DSB formation. However, roles of chromatin in meiotic DSB formation are not fully characterized. This review article summarizes our recent report showing that the conserved histone H2A variant H2A.Z promotes meiotic DSB formation in fission yeast. Through a series of experiments, we found that, in H2A.Z-lacking mutants, multiple proteins involved in DSB formation, but not cohesin subunits, are less associated with chromatin. Strikingly, nuclei were more compact in the absence of H2A.Z. These observations led us to propose that fission yeast H2A.Z promotes meiotic DSB formation partly through modulating chromosome architecture to enhance interaction between DSB-related proteins and cohesin-loaded chromatin. In addition, biological implications of our findings are discussed, and their relevance to DSB formation in other species as well as to other DNA-related events are also provided.