The SIN3A/HDAC Corepressor Complex Functionally Cooperates with NANOG to Promote Pluripotency.
The SIN3A/HDAC Corepressor Complex Functionally Cooperates with NANOG to Promote Pluripotency.
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DOI：
10.1016/j.celrep.2017.01.055
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发表时间：
2017-02-14
期刊：
影响因子：
8.8
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Saunders A;Huang X;Fidalgo M;Reimer MH Jr;Faiola F;Ding J;Sánchez-Priego C;Guallar D;Sáenz C;Li D;Wang J
尽管Sin3a是早期胚胎和胚胎干细胞（ESCs）存活所必需的，但Sin3a在维持和建立多能性中的作用尚不清楚。在这里，我们发现Sin3a/HDAC共抑制因子复合物维持ESC的多能性并促进诱导多能干细胞（iPSCs）的产生。Sin3a/HDAC共抑制复合物的成员在扩展的Nanog相互作用组中富集，并在ESCs的转录共激活中发挥作用。我们还发现了Sin3a和HDAC2在体细胞有效重编程中的关键作用。在机制上，Nanog和Sin3a在ESCs中共同占据转录活性多能基因，并且在pre-iPSCs中广泛地共定位于其全基因组靶点。此外，这两个因素都需要直接诱导协同转录程序，其中多能性基因被激活，重编程障碍基因被抑制。我们的研究结果表明，一个主要的含hdac复合物在促进多能性方面具有转录调节作用。
Although Sin3a is required for survival of early embryos and embryonic stem cells (ESCs), the role of Sin3a in the maintenance and establishment of pluripotency remains unclear. Here we find that the Sin3a/HDAC corepressor complex maintains ESC pluripotency and promotes the generation of induced pluripotent stem cells (iPSCs). Members of the Sin3a/HDAC corepressor complex are enriched in an extended Nanog interactome and function in transcriptional coactivation in ESCs. We also identified a critical role for Sin3a and HDAC2 in efficient reprogramming of somatic cells. Mechanistically, Nanog and Sin3a co-occupy transcriptionally active pluripotency genes in ESCs and also co-localize extensively at their genome-wide targets in pre-iPSCs. Additionally, both factors are required to directly induce a synergistic transcriptional program wherein pluripotency genes are activated and reprogramming barrier genes are repressed. Our findings indicate a transcriptional regulatory role for a major HDAC-containing complex in promoting pluripotency.