Master transcription factors and mediator establish super-enhancers at key cell identity genes.
Master transcription factors and mediator establish super-enhancers at key cell identity genes.
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DOI：
10.1016/j.cell.2013.03.035
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发表时间：
2013-04-11
期刊：
影响因子：
64.5
通讯作者：
Young RA
中科院分区：
文献类型：
--
作者：
Whyte WA;Orlando DA;Hnisz D;Abraham BJ;Lin CY;Kagey MH;Rahl PB;Lee TI;Young RA
主转录因子Oct4、Sox2和Nanog结合增强子元件并募集介体以激活多能胚胎干细胞（ESC）的大部分基因表达程序。我们在这里报告，ESC主转录因子形成不寻常的增强子结构域在大多数基因控制的多能状态。这些结构域，我们称之为超级增强子，由密集地被主调节子和中介子占据的增强子簇组成。超级增强子在大小、转录因子密度和含量、激活转录的能力以及对扰动的敏感性方面不同于典型增强子。Oct4或Mediator水平的降低导致超级增强子相关基因相对于其他基因的表达优先丧失，这表明基因表达程序的变化可能在发育过程中完成。在其他分化程度更高的细胞中，含有细胞类型特异性主转录因子的超级增强子也存在于定义细胞身份的基因中。因此，超级增强子在控制哺乳动物细胞身份中发挥关键作用。
Master transcription factors Oct4, Sox2 and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs). We report here that the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state. These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator. Super-enhancers differ from typical enhancers in size, transcription factor density and content, ability to activate transcription, and sensitivity to perturbation. Reduced levels of Oct4 or Mediator cause preferential loss of expression of super-enhancer-associated genes relative to other genes, suggesting how changes in gene expression programs might be accomplished during development. In other more differentiated cells, super-enhancers containing cell type-specific master transcription factors are also found at genes that define cell identity. Super-enhancers thus play key roles in the control of mammalian cell identity.
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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：
21.3
作者：
Feng, Bo;Jiang, Jianming;Ng, Huck-Hui
通讯作者：
Ng, Huck-Hui
影响因子：
21.3
作者：
Jiang, Jianming;Chan, Yun-Shen;Ng, Huck-Hui
通讯作者：
Ng, Huck-Hui
影响因子：
64.5
作者：
GROSVELD, F;VANASSENDELFT, GB;KOLLIAS, G
通讯作者：
KOLLIAS, G
影响因子：
10.5
作者：
Hu, Guang;Kim, Jonghwan;Elledge, Stephen J.
通讯作者：
Elledge, Stephen J.