Global identification of SMAD2 target genes reveals a role for multiple co-regulatory factors in zebrafish early gastrulas

Liu, Z., Lin, X., Cai, Z., Zhang, Z., Han, C., Jia, S., Meng, A., and Wang, Q.
The Journal of biological chemistry   286(32): 28520-32 (Journal)
Registered Authors
Jia, Shunji, Meng, Anming, Wang, Qiang
chromatin immunoprecepitation (CHiP), embryo, SMAD transcription factor, Transforming growth factor beta (TGFbeta), zebrafish, nodal, smad2, co-regulatory factors, gastrula
MeSH Terms
  • Animals
  • Body Patterning/physiology
  • Forkhead Transcription Factors/genetics
  • Forkhead Transcription Factors/metabolism
  • GATA Transcription Factors/genetics
  • GATA Transcription Factors/metabolism
  • Gastrula/cytology
  • Gastrula/metabolism*
  • Mesoderm/cytology
  • Mesoderm/embryology*
  • Nodal Protein/genetics
  • Nodal Protein/metabolism
  • Organic Cation Transporter 1/genetics
  • Organic Cation Transporter 1/metabolism
  • Response Elements/physiology*
  • Smad2 Protein/genetics
  • Smad2 Protein/metabolism*
  • Smad3 Protein/genetics
  • Smad3 Protein/metabolism
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Transcription, Genetic/physiology*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • beta Catenin/genetics
  • beta Catenin/metabolism
21669877 Full text @ J. Biol. Chem.
Nodal and Smad2/3 signals play pivotal roles in mesendoderm induction and axis determination during late blastulation and early gastrulation in vertebrate embryos. However, Smad2/3 direct target genes during those critical developmental stages have not been systematically identified. Here, through ChIP-chip assay, we show that the promoter/enhancer regions of 679 genes are bound by Smad2 in the zebrafish early gastrula. Expression analyses confirm that a significant proportion of Smad2 targets are indeed subjected to Nodal/Smad2 regulation at the onset of gastrulation. The co-existence of other transcription factor' DNA binding sites in the Smad2-bound regions (SBRs) allows the identification of well-known Smad2 binding partners, such as FoxH1 and Lef1/beta-catenin, as well as many previously unknown Smad2 partners, including Oct1 and Gata6, during embryogenesis. We demonstrate that Oct1 physically associates with and enhances the transcription and mesendodermal induction activity of Smad2 whereas Gata6 exerts an inhibitory role in Smad2 signaling and mesendodermal induction. Thus, our study systemically uncovers a large number of Smad2 targets in early gastrulas and suggests cooperative roles of Smad2 and other transcription factors in controlling target gene transcription, which will be valuable for studying regulatory cascades during germ layer formation and patterning of vertebrate embryos
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes