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
Inserm U823, université Joseph-Fourier, institut Albert-Bonniot, domaine de la Merci, 38706 Grenoble, France.
Gynecol Obstet Fertil. 2009 Jun;37(6):519-22. doi: 10.1016/j.gyobfe.2009.04.003. Epub 2009 May 17.
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.
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。