HEB and E2A function as SMAD/FOXH1 cofactors.
Genes Dev, 2011/8/01;25(15):1654-61.
Yoon SJ[1], Wills AE, Chuong E, Gupta R, Baker JC
Affiliations
PMID: 21828274DOI: 10.1101/gad.16800511
Impact factor: 12.89
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.
MeSH terms
Amino Acid Motifs; Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Line; Chromatin Immunoprecipitation; Embryonic Stem Cells; Endoderm; Forkhead Transcription Factors; Gastrulation; Gene Expression Regulation, Developmental; High-Throughput Nucleotide Sequencing; Humans; Left-Right Determination Factors; Protein Binding; Signal Transduction; Smad Proteins, Receptor-Regulated; Xenopus
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