Epigenomic analysis of multilineage differentiation of human embryonic stem cells.
Epigenomic analysis of multilineage differentiation of human embryonic stem cells.
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DOI：
10.1016/j.cell.2013.04.022
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发表时间：
2013-05-23
期刊：
影响因子：
64.5
通讯作者：
Ren B
中科院分区：
文献类型：
--
作者：
Xie W;Schultz MD;Lister R;Hou Z;Rajagopal N;Ray P;Whitaker JW;Tian S;Hawkins RD;Leung D;Yang H;Wang T;Lee AY;Swanson SA;Zhang J;Zhu Y;Kim A;Nery JR;Urich MA;Kuan S;Yen CA;Klugman S;Yu P;Suknuntha K;Propson NE;Chen H;Edsall LE;Wagner U;Li Y;Ye Z;Kulkarni A;Xuan Z;Chung WY;Chi NC;Antosiewicz-Bourget JE;Slukvin I;Stewart R;Zhang MQ;Wang W;Thomson JA;Ecker JR;Ren B
已经提出了表观遗传机制在哺乳动物的发展中起着至关重要的作用，但是仅部分理解其精确的功能。为了研究胚胎发育的表观遗传调节，我们将人类胚胎干细胞分化为中胚层，神经祖细胞，滋养细胞样细胞和间质干细胞，并系统地表征了DNA甲基化，染色质修饰和每个谱系中的转录组。我们发现，在早期发育阶段活跃的启动子倾向于富含CG，并且在无表达的谱系中沉默后主要参与H3K27ME3。相比之下，在以后阶段优先表达的基因的启动子通常是CG较差，并且在抑制后主要采用DNA甲基化。有趣的是，早期发育调节基因通常位于大多数谱系中通常没有DNA甲基化的大型基因组域中，我们称之为DNA甲基化谷（DMVS）。我们的结果表明，不同的表观遗传机制调节ES细胞分化的早期和晚期。
Epigenetic mechanisms have been proposed to play crucial roles in mammalian development, but their precise functions are only partially understood. To investigate epigenetic regulation of embryonic development, we differentiated human embryonic stem cells into mesendoderm, neural progenitor cells, trophoblast-like cells, and mesenchymal stem cells, and systematically characterized DNA methylation, chromatin modifications, and the transcriptome in each lineage. We found that promoters that are active in early developmental stages tend to be CG rich and mainly engage H3K27me3 upon silencing in non-expressing lineages. By contrast, promoters for genes expressed preferentially at later stages are often CG poor and primarily employ DNA methylation upon repression. Interestingly, the early developmental regulatory genes are often located in large genomic domains that are generally devoid of DNA methylation in most lineages, which we termed DNA methylation valleys (DMVs). Our results suggest that distinct epigenetic mechanisms regulate early and late stages of ES cell differentiation.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
64.5
作者：
Gifford CA;Ziller MJ;Gu H;Trapnell C;Donaghey J;Tsankov A;Shalek AK;Kelley DR;Shishkin AA;Issner R;Zhang X;Coyne M;Fostel JL;Holmes L;Meldrim J;Guttman M;Epstein C;Park H;Kohlbacher O;Rinn J;Gnirke A;Lander ES;Bernstein BE;Meissner A
通讯作者：
Meissner A
影响因子：
30.8
作者：
Kunarso, Galih;Chia, Na-Yu;Bourque, Guillaume
通讯作者：
Bourque, Guillaume
影响因子：
64.5
作者：
Lee, TI;Jenner, RG;Young, RA
通讯作者：
Young, RA
影响因子：
46.9
作者：
Chambers, Stuart M.;Fasano, Christopher A.;Papapetrou, Eirini P.;Tomishima, Mark;Sadelain, Michel;Studer, Lorenz
通讯作者：
Studer, Lorenz