Pluripotency factors and Polycomb Group proteins repress aryl hydrocarbon receptor expression in murine embryonic stem cells.
Pluripotency factors and Polycomb Group proteins repress aryl hydrocarbon receptor expression in murine embryonic stem cells.
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DOI：
10.1016/j.scr.2013.11.007
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发表时间：
2014-01
影响因子：
1.2
通讯作者：
Puga, Alvaro
中科院分区：
文献类型：
--
作者：
Ko, Chia-I;Wang, Qin;Fan, Yunxia;Xia, Ying;Puga, Alvaro
芳香烃受体（aryl hydrocarbon receptor，AHR）是一种转录因子和环境传感器，其调节参与药物代谢和细胞周期调节的基因的表达。染色质免疫沉淀分析、小鼠Ahr消融和无脊椎动物orthopathy基因研究表明，AHR也可能在胚胎发育中发挥重要作用。为了解决这一假设，我们研究了小鼠胚胎干细胞及其分化后代中Ahr表达的调控。在ES细胞中，OCT 3/4、NANOG、SOX 2和Polycomb Group蛋白在Ahr启动子处的相互作用抑制AHR表达，这也可以通过肝癌细胞中重编程因子的异位表达来抑制。在ES细胞中，非生产性RNA聚合酶II结合在Ahr转录起始位点，并驱动短的流产转录本的合成。分化过程中Ahr表达的激活来自Ahr启动子染色质中抑制标记的逆转、多能性因子和PcG蛋白的释放、Sp因子的结合、开放染色质的组蛋白标记的建立以及活性RNAPII的参与以驱动全长RNA转录物延伸。我们的研究结果表明，可逆的Ahr抑制在ES细胞保持基因的表达准备，并允许在胚胎发育过程中快速切换到激活。
The aryl hydrocarbon receptor (AHR) is a transcription factor and environmental sensor that regulates expression of genes involved in drug-metabolism and cell cycle regulation. Chromatin immunoprecipitation analyses, Ahr ablation in mice and studies with orthologous genes in invertebrates suggest that AHR may also play a significant role in embryonic development. To address this hypothesis, we studied the regulation of Ahr expression in mouse embryonic stem cells and their differentiated progeny. In ES cells, interactions between OCT3/4, NANOG, SOX2 and Polycomb Group proteins at the Ahr promoter repress AHR expression, which can also be repressed by ectopic expression of reprogramming factors in hepatoma cells. In ES cells, unproductive RNA polymerase II binds at the Ahr transcription start site and drives the synthesis of short abortive transcripts. Activation of Ahr expression during differentiation follows from reversal of repressive marks in Ahr promoter chromatin, release of pluripotency factors and PcG proteins, binding of Sp factors, establishment of histone marks of open chromatin, and engagement of active RNAPII to drive full-length RNA transcript elongation. Our results suggest that reversible Ahr repression in ES cells holds the gene poised for expression and allows for a quick switch to activation during embryonic development.
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影响因子：
5.3
作者：
GILMOUR, DS;LIS, JT
通讯作者：
LIS, JT
影响因子：
23.9
作者：
Brookes, Emily;de Santiago, Ines;Hebenstreit, Daniel;Morris, Kelly J.;Carroll, Tom;Xie, Sheila Q.;Stock, Julie K.;Heidemann, Martin;Eick, Dirk;Nozaki, Naohito;Kimura, Hiroshi;Ragoussis, Jiannis;Teichmann, Sarah A.;Pombo, Ana
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Pombo, Ana
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5.2
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Galvin-Burgess, Katherine E.;Travis, Emily D.;Pierson, Kelsey E.;Vivian, Jay L.
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Vivian, Jay L.
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
3.1
作者：
Fitzgerald, CT;Nebert, DW;Puga, A
通讯作者：
Puga, A