Department of Internal Medicine, University of Michigan Medical School, 109 Zina Pitcher Place, BSRB 1520, Ann Arbor, MI 48109, USA.
Dev Cell. 2010 Mar 16;18(3):371-84. doi: 10.1016/j.devcel.2010.01.010. Epub 2010 Feb 11.
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 postmeiotic 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.
在精子发生过程中，组蛋白最初被转换蛋白取代，随后被鱼精蛋白取代，从而发生全基因组核小体去除。这种染色质重排被认为有助于将父本基因组浓缩到精子头部，并保护 DNA 免受损伤。组蛋白泛素化被认为对减数分裂前期的性染色体失活和减数分裂后阶段的核小体去除很重要。然而，调节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 在精子发生中的作用，发现 RNF8 缺陷小鼠在减数分裂性染色体失活（MSCI）中表现出色，但在全基因组核小体去除中表现出缺陷。此外，我们表明 RNF8 依赖性组蛋白泛素化诱导 H4K16 乙酰化，这可能是核小体去除的初始步骤。因此，我们的结果表明，RNF8 通过组蛋白泛素化在精子发生中发挥重要作用，导致跨组蛋白乙酰化和全基因组核小体去除。
