在精子发育过程中,正常情况下与DNA结合、将其包裹进染色质中的组蛋白大部分被交换成鱼精蛋白,后者是形成正常精子功能所需的紧凑DNA结构的小蛋白。于是,核小体(染色质中含组蛋白的重复单元)在精子中明显罕见。虽然罕见,但根据一项利用高分辨率基因组技术来定位人成熟精子中所保留的核小体的研究工作,它们却有潜在重要性。保留下来的少数核小体所含具有极为重要发育功能的基因显著增多,而且具有鲜明的组蛋白修饰模式。这一发现提出一个可能性:它们之所以被保留下来,是为了在胚胎中执行一种表观遗传功能。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 460, 473-478 (23 July 2009) | doi:10.1038/nature08162
Distinctive chromatin in human sperm packages genes for embryo development
Saher Sue Hammoud1,2, David A. Nix3, Haiying Zhang1, Jahnvi Purwar1, Douglas T. Carrell2 & Bradley R. Cairns1
1 Howard Hughes Medical Institute, Department of Oncological Sciences, and Huntsman Cancer Institute,
2 IVF and Andrology Laboratories, Departments of Surgery, Obstetrics and Gynecology, and Physiology,
3 Research Informatics and Bioinformatics Core Facility, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA
Because nucleosomes are widely replaced by protamine in mature human sperm, the epigenetic contributions of sperm chromatin to embryo development have been considered highly limited. Here we show that the retained nucleosomes are significantly enriched at loci of developmental importance, including imprinted gene clusters, microRNA clusters, HOX gene clusters, and the promoters of stand-alone developmental transcription and signalling factors. Notably, histone modifications localize to particular developmental loci. Dimethylated lysine 4 on histone H3 (H3K4me2) is enriched at certain developmental promoters, whereas large blocks of H3K4me3 localize to a subset of developmental promoters, regions in HOX clusters, certain noncoding RNAs, and generally to paternally expressed imprinted loci, but not paternally repressed loci. Notably, trimethylated H3K27 (H3K27me3) is significantly enriched at developmental promoters that are repressed in early embryos, including many bivalent (H3K4me3/H3K27me3) promoters in embryonic stem cells. Furthermore, developmental promoters are generally DNA hypomethylated in sperm, but acquire methylation during differentiation. Taken together, epigenetic marking in sperm is extensive, and correlated with developmental regulators.