Epigenetic priming of enhancers predicts developmental competence of hESC-derived endodermal lineage intermediates.
Epigenetic priming of enhancers predicts developmental competence of hESC-derived endodermal lineage intermediates.
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DOI：
10.1016/j.stem.2015.02.013
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发表时间：
2015-04-02
期刊：
影响因子：
23.9
通讯作者：
Sander, Maike
中科院分区：
文献类型：
--
作者：
Wang, Allen;Yue, Feng;Li, Yan;Xie, Ruiyu;Harper, Thomas;Patel, Nisha A.;Muth, Kayla;Palmer, Jeffrey;Qiu, Yunjiang;Wang, Jinzhao;Lam, Dieter K.;Raum, Jeffrey C.;Stoffers, Doris A.;Ren, Bing;Sander, Maike
胚胎发育依赖于祖细胞对诱导信号做出适当反应的能力;这种细胞特性被称为发育能力。在这里，我们报告增强子的表观遗传启动意味着内胚谱系多样化期间的发育能力。人胚胎干细胞胰腺和肝脏分化过程中的染色质图谱显示，在肠管中间体中内胚层来源的细胞谱系特异性增强子处，稳定的染色质状态被增强。实验上，这种平衡增强子状态的获得预示了内胚层中间体对诱导信号作出反应的能力。此外，当获得感受态时，这些增强子首先被先驱转录因子FOXA 1和FOXA 2识别，而随后招募谱系诱导转录因子，如PDX 1，导致增强子和靶基因激活。总之，我们的研究结果确定收购的一个平衡的染色质状态增强祖细胞获得发育能力的机制。
Embryonic development relies on the capacity of progenitor cells to appropriately respond to inductive cues; a cellular property known as developmental competence. Here we report that epigenetic priming of enhancers signifies developmental competence during endodermal lineage diversification. Chromatin mapping during pancreatic and hepatic differentiation of human embryonic stem cells revealed the en masse acquisition of a poised chromatin state at enhancers specific to endoderm-derived cell lineages in gut tube intermediates. Experimentally, the acquisition of this poised enhancer state predicts the ability of endodermal intermediates to respond to inductive signals. Furthermore, these enhancers are first recognized by the pioneer transcription factors FOXA1 and FOXA2 when competence is acquired, while subsequent recruitment of lineage-inductive transcription factors, such as PDX1, leads to enhancer and target gene activation. Together, our results identify the acquisition of a poised chromatin state at enhancers as a mechanism by which progenitor cells acquire developmental competence.
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影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
64.8
作者：
JONSSON, J;CARLSSON, L;EDLUND, H
通讯作者：
EDLUND, H
影响因子：
11.4
作者：
Carr, A;Biggin, MD
通讯作者：
Biggin, MD
DOI：
10.1073/pnas.1017214108
发表时间：
2011-03-29
影响因子：
11.1
作者：
Jin, Fulai;Li, Yan;Natarajan, Rama
通讯作者：
Natarajan, Rama
影响因子：
4.5
作者：
Boj, Sylvia F.;Petrov, Dimitri;Ferrer, Jorge
通讯作者：
Ferrer, Jorge