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在. 减数分裂过程中 H2A.Z 组蛋白变体的功能影响

Functional Impact of the H2A.Z Histone Variant During Meiosis in .

机构信息

Institute of Functional Biology and Genomics, Consejo Superior de Investigaciones Científicas and University of Salamanca, 37007 Salamanca, Spain.

Department of Genome Biology, Centro Andaluz de Biología Molecular y Medicina Regenerativa, Consejo Superior de Investigaciones Científicas and University of Seville and University Pablo de Olavide, 41092 Seville, Spain.

出版信息

Genetics. 2018 Aug;209(4):997-1015. doi: 10.1534/genetics.118.301110. Epub 2018 May 31.

Abstract

Among the collection of chromatin modifications that influence its function and structure, the substitution of canonical histones by the so-called histone variants is one of the most prominent actions. Since crucial meiotic transactions are modulated by chromatin, here we investigate the functional contribution of the H2A.Z histone variant during both unperturbed meiosis and upon challenging conditions where the meiotic recombination checkpoint is triggered in budding yeast by the absence of the synaptonemal complex component Zip1 We have found that H2A.Z localizes to meiotic chromosomes in an SWR1-dependent manner. Although meiotic recombination is not substantially altered, the mutant (lacking H2A.Z) shows inefficient meiotic progression, impaired sporulation, and reduced spore viability. These phenotypes are likely accounted for by the misregulation of meiotic gene expression landscape observed in In the mutant, the absence of H2A.Z results in a tighter meiotic arrest imposed by the meiotic recombination checkpoint. We have found that Mec1-dependent Hop1-T318 phosphorylation and the ensuing Mek1 activation are not significantly altered in ; however, downstream checkpoint targets, such as the meiosis I-promoting factors Ndt80, Cdc5, and Clb1, are drastically downregulated. The study of the checkpoint response in has also allowed us to reveal the existence of an additional function of the Swe1 kinase, independent of CDK inhibitory phosphorylation, which is relevant to restrain meiotic cell cycle progression. In summary, our study shows that the H2A.Z histone variant impacts various aspects of meiotic development adding further insight into the relevance of chromatin dynamics for accurate gametogenesis.

摘要

在影响染色质功能和结构的修饰组中,组蛋白变体取代经典组蛋白是最显著的作用之一。由于关键的减数分裂事件受到染色质的调节,我们在这里研究 H2A.Z 组蛋白变体在未受干扰的减数分裂和在触发减数分裂重组检查点的情况下的功能贡献,酵母中联会复合体成分 Zip1 的缺失会导致这种情况。我们发现 H2A.Z 以 SWR1 依赖的方式定位到减数分裂染色体上。虽然减数分裂重组没有明显改变,但 突变体(缺乏 H2A.Z)表现出低效的减数分裂进程、受损的孢子形成和降低的孢子活力。这些表型可能是由于在 突变体中观察到减数基因表达图谱的失调所致。在 突变体中,由于减数分裂重组检查点的存在,H2A.Z 的缺失导致更紧密的减数分裂停滞。我们发现,Mec1 依赖性 Hop1-T318 磷酸化和随之而来的 Mek1 激活在 中没有明显改变;然而,下游检查点靶标,如促进减数分裂 I 的因子 Ndt80、Cdc5 和 Clb1,被急剧下调。对 中检查点反应的研究也使我们能够揭示 Swe1 激酶的另一个功能,该功能独立于 CDK 抑制性磷酸化,对于限制减数分裂细胞周期进程是相关的。总之,我们的研究表明,H2A.Z 组蛋白变体影响减数分裂发育的各个方面,进一步深入了解染色质动力学对精确配子发生的重要性。

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