HEB and E2A function as SMAD/FOXH1 cofactors.
HEB and E2A function as SMAD/FOXH1 cofactors.
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DOI：
10.1101/gad.16800511
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发表时间：
2011-08
影响因子：
10.5
通讯作者：
Se-Jin Yoon;A. Wills;E. Chuong;Rakhi Gupta;J. Baker
中科院分区：
文献类型：
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作者：
Se-Jin Yoon;A. Wills;E. Chuong;Rakhi Gupta;J. Baker
通过SMAD转录因子介导的节点信号传导对于多能性维持和内胚层定型是必需的。我们发现了一个新的基序，称为SMAD复合物相关（SCA），这是结合SMAD 2/3/4和FOXH 1在人胚胎干细胞（hESC）和衍生的内胚层。我们证明，两个基本的螺旋-环-螺旋（bHLH）蛋白HEB和E2 A结合SCA基序重叠SMAD 2/3和FOXH 1的区域。此外，我们发现HEB和E2 A与SMAD 2/3和FOXH 1相关，表明它们在关键靶区域形成复合物。这种关联在生物学上是重要的，因为E2 A对于热带爪蟾胚胎中的中内胚层特化、原肠胚形成和Nodal信号转导至关重要。总之，E蛋白是与SMAD 2/3和FOXH 1相关的新型Nodal信号传导辅因子，并且是中内胚层分化所必需的。
Nodal signaling, mediated through SMAD transcription factors, is necessary for pluripotency maintenance and endoderm commitment. We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. We demonstrate that two basic helix-loop-helix (bHLH) proteins-HEB and E2A-bind the SCA motif at regions overlapping SMAD2/3 and FOXH1. Furthermore, we show that HEB and E2A associate with SMAD2/3 and FOXH1, suggesting they form a complex at critical target regions. This association is biologically important, as E2A is critical for mesendoderm specification, gastrulation, and Nodal signal transduction in Xenopus tropicalis embryos. Taken together, E proteins are novel Nodal signaling cofactors that associate with SMAD2/3 and FOXH1 and are necessary for mesendoderm differentiation.