Functional Roles of Acetylated Histone Marks at Mouse Meiotic Recombination Hot Spots
Functional Roles of Acetylated Histone Marks at Mouse Meiotic Recombination Hot Spots
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DOI：
10.1128/mcb.00942-15
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发表时间：
2017-02-01
影响因子：
5.3
通讯作者：
Bois, Philippe R. J.
中科院分区：
文献类型：
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作者：
Getun, Irina V.;Wu, Zhen;Bois, Philippe R. J.
减数分裂重组开始于DNA双链断裂（DSBs）的形成，由Spo11核酸内切酶在I前期早期，在基因组的离散区域被称为“热点”。在哺乳动物中，减数分裂DSB位点选择部分是由多态组蛋白H3 （H3K4Me3）甲基转移酶PRDM9的序列特异性结合指导的。然而，减数分裂热点规范所需的其他染色质特征在很大程度上是未知的。本研究表明，小鼠活跃热点的重组核心含有几个组蛋白H3和H4乙酰化和甲基化标记，这些标记是开放的、活跃的染色质的典型特征。此外，这些开放的染色质相关组蛋白标记的沉积是动态的，并在精原细胞和/或瘦素前期细胞中表现出来，这促进了PRDM9的结合和Spo11的进入，从而指导瘦素阶段启动的dsb的形成。重要的是，通过控制组蛋白乙酰化酶和去乙酰化酶的活性，证实了组蛋白乙酰化标记对于热点活性和交叉分辨率都是必要的。我们认为组蛋白乙酰化标记在哺乳动物减数分裂重组热点中具有功能作用。
Meiotic recombination initiates following the formation of DNA doublestrand breaks (DSBs) by the Spo11 endonuclease early in prophase I, at discrete regions in the genome coined "hot spots." In mammals, meiotic DSB site selection is directed in part by sequence-specific binding of PRDM9, a polymorphic histone H3 (H3K4Me3) methyltransferase. However, other chromatin features needed for meiotic hot spot specification are largely unknown. Here we show that the recombinogenic cores of active hot spots in mice harbor several histone H3 and H4 acetylation and methylation marks that are typical of open, active chromatin. Further, deposition of these open chromatin-associated histone marks is dynamic and is manifest at spermatogonia and/or pre-leptotene-stage cells, which facilitates PRDM9 binding and access for Spo11 to direct the formation of DSBs, which are initiated at the leptotene stage. Importantly, manipulating histone acetylase and deacetylase activities established that histone acetylation marks are necessary for both hot spot activity and crossover resolution. We conclude that there are functional roles for histone acetylation marks at mammalian meiotic recombination hot spots.