Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition.
Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition.
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小鼠卵母细胞中广泛的组蛋白H3K4me3结构域调节母细胞到合子的转变
DOI：
10.1038/nature19360
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发表时间：
2016-09-22
期刊：
影响因子：
64.8
通讯作者：
Klungland A
中科院分区：
文献类型：
--
作者：
Dahl JA;Jung I;Aanes H;Greggains GD;Manaf A;Lerdrup M;Li G;Kuan S;Li B;Lee AY;Preissl S;Jermstad I;Haugen MH;Suganthan R;Bjørås M;Hansen K;Dalen KT;Fedorcsak P;Ren B;Klungland A
母体到合子的转变（MZT）是新个体形成的必要条件，尽管最近对早期胚胎发生中基因表达和DNA甲基化的分析取得了进展，但对其仍知之甚少。动态组蛋白修饰可能在MZT中起重要作用，但由于技术上的困难，对少量细胞的组蛋白修饰进行分析，阻碍了对染色质状态的直接测量。最近的改进允许每个反应500个细胞当量的染色质，但需要10,000个细胞进行初始步骤或需要高度专业化的微流体设备，这是不容易获得的。我们建立了一种微尺度染色质免疫沉淀和测序（μChlP-seq）方法，用于分析小鼠未成熟卵母细胞和中期卵母细胞以及2细胞和8细胞胚胎的全基因组组蛋白H3赖氨酸甲基化（H3K4me3）和乙酰化（H3K27ac）。值得注意的是，我们发现约22%的卵母细胞基因组与广泛的H3K4me3结构域相关，这些结构域与DNA甲基化抗相关。H3K4me3信号在2细胞胚胎中局限于转录起始位点区域，伴随着主要合子基因组激活的开始。赖氨酸去甲基酶KDM5A和KDM5B主动去除广泛的H3K4me3结构域是正常的合子基因组激活所必需的，也是早期胚胎发育所必需的。我们的研究结果为小鼠胚胎发育程序的开始提供了见解，并证明了广泛的H3K4me3结构域在MZT中的作用。
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 embryogenesis. Dynamic histone modifications may have important roles in MZT, 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 steps or require a highly specialized microfluidics device that is not readily available. We developed a micro-scale chromatin immunoprecipitation and sequencing (μChlP-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.
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影响因子：
10.5
作者：
Park SJ;Komata M;Inoue F;Yamada K;Nakai K;Ohsugi M;Shirahige K
通讯作者：
Shirahige K
影响因子：
64.5
作者：
Benayoun BA;Pollina EA;Ucar D;Mahmoudi S;Karra K;Wong ED;Devarajan K;Daugherty AC;Kundaje AB;Mancini E;Hitz BC;Gupta R;Rando TA;Baker JC;Snyder MP;Cherry JM;Brunet A
通讯作者：
Brunet A
影响因子：
14.8
作者：
Dahl, John Arne;Collas, Philippe
通讯作者：
Collas, Philippe
DOI：
10.1007/978-1-62703-191-2_17
发表时间：
2013-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Chiang, Teresa;Lampson, Michael A
通讯作者：
Lampson, Michael A
DOI：
10.1007/978-1-4939-1594-1_17
发表时间：
2015-01-01
期刊：
NUCLEAR REPROGRAMMING: METHODS AND PROTOCOLS, 2ND EDITION
影响因子：
--
作者：
Dahl, John Arne;Klungland, Arne
通讯作者：
Klungland, Arne