Bivalent chromatin marks developmental regulatory genes in the mouse embryonic germline in vivo.
Bivalent chromatin marks developmental regulatory genes in the mouse embryonic germline in vivo.
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DOI：
10.1016/j.celrep.2013.04.032
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发表时间：
2013-06-27
期刊：
影响因子：
8.8
通讯作者：
Ramalho-Santos M
中科院分区：
文献类型：
--
作者：
Sachs M;Onodera C;Blaschke K;Ebata KT;Song JS;Ramalho-Santos M
发育调控基因在胚胎干细胞（ESC）中具有激活（H3 K4 me 3）和抑制（H3 K27 me 3）组蛋白修饰。这种二价结构被认为是保持血统承诺程序处于平衡状态。然而，由于染色质免疫沉淀（ChIP）所需的大量细胞，建立生理相关性变得复杂。我们开发了一种低细胞数染色质免疫沉淀（低细胞ChIP）协议，以调查小鼠原始生殖细胞（PGCs）的染色质。胚胎第11.5天（E11.5）PGCs的全基因组分析显示H3 K4 me 3/H3 K27 me 3二价结构域高度富集在发育调控基因的方式非常相似的ESC。发育调节剂保持二价和转录沉默，通过启动性分化在E13.5。我们还鉴定了> 2，500个“孤儿”二价结构域，其远离已知基因并且以组织特异性方式表达但在PGCs中沉默。我们的研究结果表明，存在的二价结构域的种系和提高的可能性，体细胞程序是持续保持为二价，潜在地赋予跨代表观遗传。
Developmental regulatory genes have both activating (H3K4me3) and repressive (H3K27me3) histone modifications in embryonic stem cells (ESCs). This bivalent configuration is thought to maintain lineage commitment programs in a poised state. However, establishing physiological relevance has been complicated by the high number of cells required for chromatin immunoprecipitation (ChIP). We developed a low-cell-number chromatin immunoprecipitation (low-cell ChIP) protocol to investigate the chromatin of mouse primordial germ cells (PGCs). Genome-wide analysis of embryonic day 11.5 (E11.5) PGCs revealed H3K4me3/H3K27me3 bivalent domains highly enriched at developmental regulatory genes in a manner remarkably similar to ESCs. Developmental regulators remain bivalent and transcriptionally silent through the initiation of sexual differentiation at E13.5. We also identified >2,500 "orphan" bivalent domains that are distal to known genes and expressed in a tissue-specific manner but silent in PGCs. Our results demonstrate the existence of bivalent domains in the germline and raise the possibility that the somatic program is continuously maintained as bivalent, potentially imparting transgenerational epigenetic inheritance.
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影响因子：
64.8
作者：
Hajkova, Petra;Ancelin, Katia;Waldmann, Tanja;Lacoste, Nicolas;Lange, Ulrike C.;Cesari, Francesca;Lee, Caroline;Almouzni, Genevieve;Schneider, Robert;Surani, M. Azim
通讯作者：
Surani, M. Azim
影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
64.5
作者：
Goldberg AD;Banaszynski LA;Noh KM;Lewis PW;Elsaesser SJ;Stadler S;Dewell S;Law M;Guo X;Li X;Wen D;Chapgier A;DeKelver RC;Miller JC;Lee YL;Boydston EA;Holmes MC;Gregory PD;Greally JM;Rafii S;Yang C;Scambler PJ;Garrick D;Gibbons RJ;Higgs DR;Cristea IM;Urnov FD;Zheng D;Allis CD
通讯作者：
Allis CD
影响因子：
4.6
作者：
Alder, Olivia;Lavial, Fabrice;Azuara, Veronique
通讯作者：
Azuara, Veronique
影响因子：
14.8
作者：
Dahl, John Arne;Collas, Philippe
通讯作者：
Collas, Philippe