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Nature:美教授发表组蛋白调控功能研究成果

摘要 : 2016年9月14日,国际学术权威刊物自然出版集团旗下子刊《Nature》杂志在线发表了加州大学任兵教授研究组、奥斯陆大学Arne Klungland教授和John Arne Dahl教授合作的一篇研究论文,论文揭示了组蛋白H3K4me3对小鼠卵母细胞MZT的调节作用。

 2016年9月14日,国际学术权威刊物自然出版集团旗下子刊《Nature》杂志在线发表了加州大学的任兵教授研究组、奥斯陆大学的Arne Klungland教授和John Arne Dahl教授合作的一篇研究论文,论文揭示了组蛋白H3K4me3对小鼠卵母细胞MZT的调节作用。

母型-合子型转变(MZT)对于新个体形成是必不可少的。虽然早期胚胎发育的基因表达和DNA甲基化分析已经取得了不少进展,但人们对MZT过程依然知之甚少。

动态的组蛋白修饰可能在MZT中起到了重要作用。不过,测定小量细胞的组蛋白修饰图谱还比较困难。目前的检测反应一次可以处理500个细胞的染色质,但起始步骤需要一万个细胞,不然就得使用专业的微流体设备。

任兵教授及其同事为此开发了微尺度的染色质免疫沉淀测序(μChIP–seq)。他们用这种方法分析小鼠的不成熟卵母细胞、MII期卵母细胞、2-细胞胚胎和8-细胞胚胎,获得了组蛋白甲基化H3K4me3和组蛋白乙酰化H3K27ac的全基因组图谱。

研究显示,卵母细胞大约22%的基因组存在宽H3K4me3修饰区域。而2-细胞胚胎的H3K4me3信号变得仅限于转录起始区域,这伴随着合子基因组激活。研究指出,合子基因组正常激活和早期胚胎正常发育,需要赖氨酸去甲基化酶KDM5A和KDM5B积极去除宽H3K4me3修饰区域。

原文链接:

Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition

原文摘要:

Maternal-to-zygotic transition (MZT) is essential for the formation of a new individual, but is still poorly understood despite recent progress in analysis of gene expression and DNA methylation in early embryogenesis1, 2, 3, 4, 5, 6, 7, 8, 9. Dynamic histone modifications may have important roles in MZT10, 11, 12, 13, but direct measurements of chromatin states have been hindered by technical difficulties in profiling histone modifications from small quantities of cells. Recent improvements allow for 500 cell-equivalents of chromatin per reaction, but require 10,000 cells for initial steps14 or require a highly specialized microfluidics device that is not readily available15. We developed a micro-scale chromatin immunoprecipitation and sequencing (μChIP–seq) method, which we used to profile genome-wide histone H3 lysine methylation (H3K4me3) and acetylation (H3K27ac) in mouse immature and metaphase II oocytes and in 2-cell and 8-cell embryos. Notably, we show that ~22% of the oocyte genome is associated with broad H3K4me3 domains that are anti-correlated with DNA methylation. The H3K4me3 signal becomes confined to transcriptional-start-site regions in 2-cell embryos, concomitant with the onset of major zygotic genome activation. Active removal of broad H3K4me3 domains by the lysine demethylases KDM5A and KDM5B is required for normal zygotic genome activation and is essential for early embryo development. Our results provide insight into the onset of the developmental program in mouse embryos and demonstrate a role for broad H3K4me3 domains in MZT.

来源: Nature 浏览次数:0

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