Nono, a Bivalent Domain Factor, Regulates Erk Signaling and Mouse Embryonic Stem Cell Pluripotency.

Nono, a Bivalent Domain Factor, Regulates Erk Signaling and Mouse Embryonic Stem Cell Pluripotency.
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DOI:
10.1016/j.celrep.2016.09.078
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发表时间:
2016-10-18
期刊:
影响因子:
8.8
通讯作者:
Shi Y
Shi Y
中科院分区:
生物学1区
文献类型:
--
作者:
Ma C;Karwacki-Neisius V;Tang H;Li W;Shi Z;Hu H;Xu W;Wang Z;Kong L;Lv R;Fan Z;Zhou W;Yang P;Wu F;Diao J;Tan L;Shi YG;Lan F;Shi Y

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Nono是para-speckle的一个组成部分,它存储和处理RNA。小鼠胚胎干细胞(mESC)缺乏para-speckles,使得Nono在mESC中的功能尚不清楚。在这里,我们发现Nono作为染色质调节剂与Erk合作调节mESC多能性。我们报告说,Nono损失的结果在强大的自我更新mESC与表观基因组和转录组学的功能类似的2i(GSK和Erk抑制剂)诱导的“基态”。Erk与Nono相互作用,并且是Nono定位于具有高水平的稳定RNA聚合酶的二价基因子集所必需的。Nono损失损害Erk活化和RNA聚合酶在未分化的mESC中在其靶二价基因处的平衡;从而破坏靶基因活化和分化。这些研究结果表明,Nono与Erk信号传导合作,调节二价结构域的完整性和mESC多能性。
Nono is a component of the para-speckle, which stores and processes RNA. Mouse embryonic stem cells (mESCs) lack para-speckles, leaving the function of Nono in mESCs unclear. Here we find that Nono functions as a chromatin regulator cooperating with Erk to regulate mESC pluripotency. We report that Nono loss results in robust self-renewing mESCs with epigenomic and transcriptomic features resembling the 2i (GSK and Erk inhibitors)-induced “ground state”. Erk interacts with and is required for Nono localization to a subset of bivalent genes that have high levels of poised RNA polymerase. Nono loss compromises Erk activation and RNA polymerase poising at its target bivalent genes in undifferentiated mESCs; thus disrupting target gene activation and differentiation. These findings argue that Nono collaborates with Erk signaling to regulate the integrity of bivalent domains and mESC pluripotency.
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