PDF(Pubmed)
Abstract：
SOX2 is a transcription factor involved in the regulatory network maintaining the pluripotency of embryonic stem cells in culture as well as in early embryos. In addition, SOX2 plays a pivotal role in neural stem cell formation and neurogenesis. How SOX2 can serve both processes has remained elusive. Here, we identified a set of SOX2-dependent neural-associated enhancers required for neural lineage priming. They form a distinct subgroup (1,898) among 8,531 OCT4/SOX2/NANOG-bound enhancers characterized by enhanced SOX2 binding and chromatin accessibility. Activation of these enhancers is triggered by neural induction of wild-type cells or by default in Smad4-ablated cells resistant to mesoderm induction and is antagonized by mesodermal transcription factors via Sox2 repression. Our data provide mechanistic insight into the transition from the pluripotency state to the early neural fate and into the regulation of early neural versus mesodermal specification in embryonic stem cells and embryos.
摘要：
S0X2是参与维持培养以及早期胚胎中胚胎干细胞多能性的调控网络的转录因子。此外,SOX2在神经干细胞形成和神经发生中起关键作用。SOX2如何为这两个过程服务仍然难以捉摸。这里,我们确定了神经谱系启动所需的一组SOX2依赖性神经相关增强剂.它们在8,531个OCT4/SOX2/NANOG结合的增强剂中形成一个不同的亚组(1,898),其特征在于增强的SOX2结合和染色质可接近性。这些增强子的激活由野生型细胞的神经诱导触发，或者默认情况下在对中胚层诱导具有抗性的Smad4消除细胞中触发，并通过Sox2抑制被中胚层转录因子拮抗。我们的数据提供了从多能性状态到早期神经命运的转变以及胚胎干细胞和胚胎中早期神经与中胚层规格的调节的机制见解。
