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精子发生:组蛋白乙酰化引发雄性基因组重编程

[Spermiogenesis: histone acetylation triggers male genome reprogramming].

作者信息

Rousseaux S, Gaucher J, Thevenon J, Caron C, Vitte A-L, Curtet S, Derobertis C, Faure A-K, Levy R, Aknin-Seifer I, Ravel C, Siffroi J-P, Mc Elreavey K, Lejeune H, Jimenez C, Hennebicq S, Khochbin S

机构信息

Inserm U823, université Joseph-Fourier, institut Albert-Bonniot, domaine de la Merci, 38706 Grenoble, France.

出版信息

Gynecol Obstet Fertil. 2009 Jun;37(6):519-22. doi: 10.1016/j.gyobfe.2009.04.003. Epub 2009 May 17.

DOI:10.1016/j.gyobfe.2009.04.003
PMID:19447664
Abstract

During their post-meiotic maturation, male germ cells undergo an extensive reorganization of their genome, during which histones become globally hyperacetylated, are then removed and progressively replaced by transition proteins and finally by protamines. The latter are known to tightly associate with DNA in the mature sperm cell. Although this is a highly conserved and fundamental biological process, which is a necessary prerequisite for the transmission of the male genome to the next generation, its molecular basis remains mostly unknown. We have identified several key factors involved in this process, and their detailed functional study has enabled us to propose the first model describing molecular mechanisms involved in post-meiotic male genome reprogramming. One of them, Bromodomain Testis Specific (BRDT), has been the focus of particular attention since it possesses the unique ability to specifically induce a dramatic compaction of acetylated chromatin. Interestingly, a mutation was found homozygous in infertile men which, according to our structural and functional studies, disrupts the function of the protein. A combination of molecular structural and genetic approaches has led to a comprehensive understanding of new major actors involved in the male genome reprogramming and transmission.

摘要

在减数分裂后的成熟过程中,雄性生殖细胞经历了基因组的广泛重组,在此期间,组蛋白整体发生高度乙酰化,随后被去除,并逐渐被过渡蛋白取代,最终被鱼精蛋白取代。已知后者在成熟精子细胞中与DNA紧密结合。尽管这是一个高度保守且基本的生物学过程,是雄性基因组向下一代传递的必要前提,但其分子基础大多仍不为人知。我们已经鉴定出参与这一过程的几个关键因素,对它们的详细功能研究使我们能够提出第一个描述减数分裂后雄性基因组重编程所涉及分子机制的模型。其中之一,睾丸特异性溴结构域蛋白(BRDT),因其具有特异性诱导乙酰化染色质显著压缩的独特能力而受到特别关注。有趣的是,在不育男性中发现了一个纯合突变,根据我们的结构和功能研究,该突变破坏了该蛋白的功能。分子结构和遗传学方法的结合使我们对参与雄性基因组重编程和传递的新主要因子有了全面的了解。

相似文献

1
[Spermiogenesis: histone acetylation triggers male genome reprogramming].精子发生:组蛋白乙酰化引发雄性基因组重编程
Gynecol Obstet Fertil. 2009 Jun;37(6):519-22. doi: 10.1016/j.gyobfe.2009.04.003. Epub 2009 May 17.
2
Molecular models for post-meiotic male genome reprogramming.有丝分裂后雄性基因组重编程的分子模型。
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A haploid affair: core histone transitions during spermatogenesis.单倍体事件:精子发生过程中的核心组蛋白转变
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The interaction of modified histones with the bromodomain testis-specific (BRDT) gene and its mRNA level in sperm of fertile donors and subfertile men.改良组蛋白与睾丸特异性溴结构域蛋白(BRDT)基因及其 mRNA 水平在生育能力正常和生育能力低下供体精子中的相互作用。
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Pericentric heterochromatin reprogramming by new histone variants during mouse spermiogenesis.小鼠精子发生过程中新型组蛋白变体介导的着丝粒周围异染色质重编程
J Cell Biol. 2007 Jan 29;176(3):283-94. doi: 10.1083/jcb.200604141.
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The first bromodomain of Brdt, a testis-specific member of the BET sub-family of double-bromodomain-containing proteins, is essential for male germ cell differentiation.Brdt是含双溴结构域蛋白的BET亚家族中的睾丸特异性成员,其首个溴结构域对雄性生殖细胞分化至关重要。
Development. 2007 Oct;134(19):3507-15. doi: 10.1242/dev.004481. Epub 2007 Aug 29.
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[Epigenetics of the sperm cell].[精子细胞的表观遗传学]
Gynecol Obstet Fertil. 2006 Sep;34(9):831-5. doi: 10.1016/j.gyobfe.2006.07.012. Epub 2006 Sep 1.
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Establishment of male-specific epigenetic information.雄性特异性表观遗传信息的建立。
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Proteomic strategy for the identification of critical actors in reorganization of the post-meiotic male genome.蛋白质组学策略鉴定减数分裂后雄性基因组重排的关键因子
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Combined proteomic and in silico approaches to decipher post-meiotic male genome reprogramming in mice.联合蛋白质组学和计算方法解析小鼠减数后雄性基因组重编程。
Syst Biol Reprod Med. 2012 Aug;58(4):191-6. doi: 10.3109/19396368.2012.663055.

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