E2a is necessary for Smad2/3-dependent transcription and the direct repression of lefty during gastrulation.
E2a is necessary for Smad2/3-dependent transcription and the direct repression of lefty during gastrulation.
复制标题
DOI：
10.1016/j.devcel.2014.11.034
复制
发表时间：
2015-02-09
影响因子：
11.8
通讯作者：
Baker JC
中科院分区：
文献类型：
--
作者：
Wills AE;Baker JC
转录因子复合物对细胞命运和行为有不同的影响，但这种功能的多样化是如何发生的在很大程度上是未知的。Nodal信号通路具有许多生物学功能，这些功能都集中在转录因子Smad2/3上。Smad2/3有许多辅助因子，这些辅助因子的替代使用可能提供调节Smad2/3功能的机制。在这里，我们研究了辅助因子E2a的扰动如何影响原肠胚形成过程中Smad2/3结合和基因表达的全局模式。我们发现E2a通过两种方式调控早期发育。E2a改变了Smad2/3在节点抑制剂左侧的结合位置，导致对中胚层规范至关重要的左侧的直接抑制。另外，E2a是驱动Smad2/3靶基因转录所必需的，包括背细胞命运和形态发生的关键调节因子。总的来说，我们发现E2a同时作为转录抑制因子和激活因子来精确调节节点信号。
Transcription factor complexes have varied effects on cell fate and behavior, but how this diversification of function occurs is largely unknown. The Nodal signaling pathway has many biological functions that all converge on the transcription factors Smad2/3. Smad2/3 has many cofactors, and alternative usage of these may provide a mechanism for modulating Smad2/3 function. Here we investigated how perturbation of the cofactor E2a affects global patterns of Smad2/3 binding and gene expression during gastrulation. We find that E2a regulates early development in two ways. E2a changes the position of Smad2/3 binding at the Nodal inhibitor lefty, resulting in direct repression of lefty that is critical for mesendoderm specification. Separately, E2a is necessary to drive transcription of Smad2/3 target genes, including critical regulators of dorsal cell fate and morphogenesis. Overall, we find that E2a functions as both a transcriptional repressor and activator to precisely regulate Nodal signaling.