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E2a is necessary for Smad2/3-dependent transcription and the direct repression of lefty during gastrulation.

Developmental cell | 2015

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.

Pubmed ID: 25669884 RIS Download

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM095346
  • Agency: NIGMS NIH HHS, United States
    Id: R01GM103787
  • Agency: NIGMS NIH HHS, United States
    Id: R01GM095346
  • Agency: NICHD NIH HHS, United States
    Id: R01HD076839
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM103787
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD076839
  • Agency: NIDDK NIH HHS, United States
    Id: F32 DK089643
  • Agency: NIDDK NIH HHS, United States
    Id: 1F32 DK089643-01

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Gene Expression Omnibus (GEO) (tool)

RRID:SCR_005012

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

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BEDTools (tool)

RRID:SCR_006646

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