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Genes Dev. August 1, 2011; 25 (15): 1654-61.

HEB and E2A function as SMAD/FOXH1 cofactors.

Yoon SJ , Wills AE , Chuong E , Gupta R , Baker JC .

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.

PubMed ID: 21828274
PMC ID: PMC3182016
Article link: Genes Dev.
Grant support: F32DK089643-01 NIDDK NIH HHS , T32 HG000044 NHGRI NIH HHS

Genes referenced: cer1 foxh1.2 gal.2 gapdh gsc lefty mixer nodal nodal1 odc1 smad2 smad3 smad4.1 sox17b.1 t tcf12 tcf3
Morpholinos referenced: tcf12 MO1 tcf12 MO2 tcf3 MO1

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