The histone variant H2A.Z promotes initiation of meiotic recombination in fission yeast.

The histone variant H2A.Z promotes initiation of meiotic recombination in fission yeast.
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组蛋白变体H2A.Z促进了裂变酵母中减数分裂重组的开始。

DOI:
10.1093/nar/gkx1110
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发表时间:
2018-01-25
影响因子:
14.9
通讯作者:
Yamada T
Yamada T
中科院分区:
生物学2区
文献类型:
--
作者:
Yamada S;Kugou K;Ding DQ;Fujita Y;Hiraoka Y;Murakami H;Ohta K;Yamada T

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减数分裂重组是由DNA双链断裂(DSB)的程序性形成启动的,双链断裂主要形成在重组热点。减数分裂DSB需要多种蛋白质,包括保守蛋白Spo11及其辅因子,并受染色质结构的影响。例如,热点周围的局部染色质直接影响DSB的形成。此外,DSB被认为发生在被称为轴环的高阶染色质结构中,在该结构中,许多环从富含粘附素的轴突出。然而,关于减数分裂DSB是如何在染色质中产生的,仍有许多未知之处。在这里,我们证明了保守的组蛋白H_2A变异体H_2A.Z促进分裂酵母中DSB的形成。详细的研究表明,H_2A.Z既不在热点附近,也不在轴心部位,在没有H_2A_Z的情况下,DSB促进因子的转录水平保持不变。此外,H_2A_Z对于减数分裂粘附素的染色质结合似乎是必不可少的。相反,在缺乏H2A.Z的突变体中,参与DSB形成的多种蛋白质,如分裂酵母Spo11同源物及其调节因子,与染色质的相关性较小。值得注意的是,在没有H2A.Z的情况下,细胞核更加致密。基于这些,我们认为分裂酵母H2A.Z促进减数分裂DSB的形成部分是通过调节染色体结构来增强DSB相关蛋白和粘附素负载的染色质之间的相互作用。
Meiotic recombination is initiated by programmed formation of DNA double strand breaks (DSBs), which are mainly formed at recombination hotspots. Meiotic DSBs require multiple proteins including the conserved protein Spo11 and its cofactors, and are influenced by chromatin structure. For example, local chromatin around hotspots directly impacts DSB formation. Moreover, DSB is proposed to occur in a higher-order chromatin architecture termed ‘axis-loop’, in which many loops protrude from cohesin-enriched axis. However, still much remains unknown about how meiotic DSBs are generated in chromatin. Here, we show that the conserved histone H2A variant H2A.Z promotes meiotic DSB formation in fission yeast. Detailed investigation revealed that H2A.Z is neither enriched around hotspots nor axis sites, and that transcript levels of DSB-promoting factors were maintained without H2A.Z. Moreover, H2A.Z appeared to be dispensable for chromatin binding of meiotic cohesin. Instead, in H2A.Z-lacking mutants, multiple proteins involved in DSB formation, such as the fission yeast Spo11 homolog and its regulators, were less associated with chromatin. Remarkably, nuclei were more compact in the absence of H2A.Z. Based on these, we 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.
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