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Publication : HEB and E2A function as SMAD/FOXH1 cofactors.

First Author  Yoon SJ Year  2011
Journal  Genes Dev Volume  25
Issue  15 Pages  1654-61
PubMed ID  21828274 Mgi Jnum  J:211239
Mgi Id  MGI:5574293 Doi  10.1101/gad.16800511
Citation  Yoon SJ, et al. (2011) HEB and E2A function as SMAD/FOXH1 cofactors. Genes Dev 25(15):1654-61
abstractText  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.
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