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HEB and E2A function as SMAD/FOXH1 cofactors.

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


  • Yoon SJ
  • Wills AE
  • Chuong E
  • Gupta R
  • Baker JC


Genes & development

Publication Data

August 1, 2011

Associated Grants

  • Agency: NIDDK NIH HHS, Id: F32DK089643-01

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