RNF8-dependent histone modifications regulate nucleosome removal during spermatogenesis.

RNF8-dependent histone modifications regulate nucleosome removal during spermatogenesis.
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DOI:
10.1016/j.devcel.2010.01.010
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发表时间:
2010-03-16
期刊:
影响因子:
11.8
通讯作者:
Yu, Xiaochun
Yu, Xiaochun
中科院分区:
生物学1区
文献类型:
--
作者:
Lu, Lin-Yu;Wu, Jiaxue;Ye, Lin;Gavrilina, Galina B.;Saunders, Thomas L.;Yu, Xiaochun

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在精子发生过程中,整体核小体去除发生,组蛋白最初被过渡蛋白取代,随后被精蛋白取代。这种染色质重组被认为促进了父系基因组在精子头部的压实,并保护DNA免受破坏因子的影响。组蛋白泛素化被认为是减数分裂前期性染色体失活和减数分裂后核小体去除的重要因素。然而,调控这些泛素介导过程的机制尚不清楚。在这项研究中,我们研究了泛素连接酶RNF8在精子发生过程中的作用,发现RNF8缺陷小鼠精通减数分裂性染色体失活(MSCI),但缺乏整体核小体去除。此外,我们发现依赖rnf8的组蛋白泛素化诱导H4K16乙酰化,这可能是核小体去除的第一步。因此,我们的研究结果表明,RNF8通过组蛋白泛素化在精子发生过程中发挥重要作用,导致反式组蛋白乙酰化和整体核小体去除。
During spermatogenesis, global nucleosome removal occurs where histones are initially replaced by transition proteins and subsequently by protamines. This chromatin reorganization is thought to facilitate the compaction of the paternal genome into the sperm head and to protect the DNA from damaging agents. Histone ubiquitination has been suggested to be important for sex chromosome inactivation during meiotic prophase and nucleosome removal at post-meiotic stages. However, the mechanisms regulating these ubiquitin-mediated processes are unknown. In this study, we investigate the role of the ubiquitin ligase RNF8 during spermatogenesis and find that RNF8-deficient mice are proficient in meiotic sex chromosome inactivation (MSCI), but deficient in global nucleosome removal. Moreover, we show that RNF8-dependent histone ubiquitination induces H4K16 acetylation, which may be an initial step in nucleosome removal. Thus, our results show that RNF8 plays an important role during spermatogenesis through histone ubiquitination, resulting in trans-histone acetylation and global nucleosome removal.
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