title: E2a is necessary for Smad2/3-dependent transcription and the direct repression of lefty during gastrulation.
abstract: Transcription factor complexes have varied effects on cell fate and behavior, but how this diversification of function occurs is largely unknown. The Nodal signaling pathway has many biological functions that all converge on the transcription factors Smad2/3. Smad2/3 has many cofactors, and alternative usage of these may provide a mechanism for modulating Smad2/3 function. Here, we investigate how perturbation of the cofactor E2a affects global patterns of Smad2/3 binding and gene expression during gastrulation. We find that E2a regulates early development in two ways. E2a changes the position of Smad2/3 binding at the Nodal inhibitor lefty, resulting in direct repression of lefty that is critical for mesendoderm specification. Separately, E2a is necessary to drive transcription of Smad2/3 target genes, including critical regulators of dorsal cell fate and morphogenesis. Overall, we find that E2a functions as both a transcriptional repressor and activator to precisely regulate Nodal signaling.
authors: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors: Andrea E
authors: AE
authors: Wills
authors: Department of Genetics, Stanford University, Stanford, CA 94305, USA; Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA. Electronic address: jbaker@stanford.edu.
authors: Julie C
authors: JC
authors: Baker
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004707:Endoderm / Q000378:metabolism; D054262:Gastrulation / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008648:Mesoderm / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D058127:Transcription Factor 3; D014157:Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014981:Xenopus / Q000196:embryology / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*
chemical_list: D051899:Smad2 Protein; C497785:Smad2 protein, Xenopus; D051900:Smad3 Protein; C544917:Tcf3 protein, Xenopus; D058127:Transcription Factor 3; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins