title: HEB and E2A function as SMAD/FOXH1 cofactors.
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.
authors.affiliation: Department of Genetics, Stanford University, Stanford, California 94305, USA.
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Yoon
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Wills
authors.forename: Edward
authors.initials: E
authors.lastname: Chuong
authors.forename: Rakhi
authors.initials: R
authors.lastname: Gupta
authors.forename: Julie C
authors.initials: JC
authors.lastname: Baker
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D053595:Embryonic Stem Cells; D004707:Endoderm / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D054262:Gastrulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D055458:Left-Right Determination Factors / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D051896:Smad Proteins, Receptor-Regulated / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051858:Forkhead Transcription Factors; D055458:Left-Right Determination Factors; D051896:Smad Proteins, Receptor-Regulated; C510350:FOXH1 protein, human; C407909:TCF3 protein, human; C073366:TCF12 protein, human