在精子發(fā)育過(guò)程中,,正常情況下與DNA結(jié)合,、將其包裹進(jìn)染色質(zhì)中的組蛋白大部分被交換成魚(yú)精蛋白,,后者是形成正常精子功能所需的緊湊DNA結(jié)構(gòu)的小蛋白。于是,,核小體(染色質(zhì)中含組蛋白的重復(fù)單元)在精子中明顯罕見(jiàn),。雖然罕見(jiàn),但根據(jù)一項(xiàng)利用高分辨率基因組技術(shù)來(lái)定位人成熟精子中所保留的核小體的研究工作,,它們卻有潛在重要性,。保留下來(lái)的少數(shù)核小體所含具有極為重要發(fā)育功能的基因顯著增多,而且具有鮮明的組蛋白修飾模式,。這一發(fā)現(xiàn)提出一個(gè)可能性:它們之所以被保留下來(lái),,是為了在胚胎中執(zhí)行一種表觀遺傳功能。(生物谷Bioon.com)
生物谷推薦原始出處:
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.