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Dev Cell 2015 Feb 09;323:345-57. doi: 10.1016/j.devcel.2014.11.034.
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E2a is necessary for Smad2/3-dependent transcription and the direct repression of lefty during gastrulation.

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
PMC ID: PMC4510980
Article link: Dev Cell
Grant support: [+]

Species referenced: Xenopus
Genes referenced: cdc42ep4 cer1 cox7b crx efna1 eomes epha4 fgf8 foxa2 foxa4 foxc2 foxd3 foxh1.2 frzb fzd8 gata4 gata5 gata6 gatm gs17 gsc h2bc21 hhex hpdl lefty lhx1 lpar2 map2k6 mespb myf5 myod1 nkx2-5 nodal nodal1 nr6a1 nradd nudt22 odc1 otx2 pcdh8.2 pkdcc.1 ror2 rspo2 shh slc38a3 smad2 snai1 stx6 tbxt tcf3 tsg101 vegt ventx1 wnt11 wnt5b zic3 znf703
Antibodies: GFP Ab5 Smad2 Ab9
Morpholinos: lefty MO7 tcf3 MO1

GEO Series: GSE56169: Xenbase,  NCBI

Article Images: [+] show captions
References [+] :
Bayly, E2A-PBX1 interacts directly with the KIX domain of CBP/p300 in the induction of proliferation in primary hematopoietic cells. 2004, Pubmed