HEB 和 E2A 作为 SMAD/FOXH1 共激活因子发挥作用。
HEB and E2A function as SMAD/FOXH1 cofactors.
机构信息
Department of Genetics, Stanford University, Stanford, California 94305, USA.
出版信息
Genes Dev. 2011 Aug 1;25(15):1654-61. doi: 10.1101/gad.16800511.
Abstract
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.
摘要
通过 SMAD 转录因子介导的节点信号对于维持多能性和内胚层承诺是必要的。我们鉴定了一个新的基序，称为 SMAD 复合物相关（SCA），在人胚胎干细胞（hESC）和衍生的内胚层中被 SMAD2/3/4 和 FOXH1 结合。我们证明了两个碱性螺旋-环-螺旋（bHLH）蛋白-HEB 和 E2A-在与 SMAD2/3 和 FOXH1 重叠的区域结合 SCA 基序。此外，我们表明 HEB 和 E2A 与 SMAD2/3 和 FOXH1 相关联，表明它们在关键靶区域形成复合物。这种关联具有重要的生物学意义，因为 E2A 对于中胚层的特化、原肠胚形成和 Xenopus tropicalis 胚胎中的 Nodal 信号转导至关重要。总之，E 蛋白是与 SMAD2/3 和 FOXH1 相关联的新型 Nodal 信号转导共因子，对于中胚层分化是必要的。
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