Systematic name M2356
Brief description Genes with promoters occupied by SMAD2 or SMAD3 [GeneID=4087] [GeneID=4088] in HaCaT cells (keratinocyte) according to a ChIP-chip analysis.
Full description or abstract The Smad2 and Smad3 (Smad2/3) proteins are principally involved in the transmission of transforming growth factor beta (TGF-beta) signaling from the plasma membrane to the nucleus. Many transcription factors have been shown to cooperate with the Smad2/3 proteins in regulating the transcription of target genes, enabling appropriate gene expression by cells. Here we identified 1,787 Smad2/3 binding sites in the promoter regions of over 25,500 genes by chromatin immunoprecipitation on microarray in HaCaT keratinocytes. Binding elements for the v-ets erythroblastosis virus E26 oncogene homolog (ETS) and transcription factor AP-2 (TFAP2) were significantly enriched in Smad2/3 binding sites, and knockdown of either ETS1 or TFAP2A resulted in overall alteration of TGF-beta-induced transcription, suggesting general roles for ETS1 and TFAP2A in the transcription induced by TGF-beta-Smad pathways. We identified novel Smad binding sites in the CDKN1A gene where Smad2/3 binding was regulated by ETS1 and TFAP2A. Moreover, we showed that small interfering RNAs for ETS1 and TFAP2A affected TGF-beta-induced cytostasis. We also analyzed Smad2- or Smad3-specific target genes regulated by TGF-beta and found that their specificity did not appear to be solely determined by the amounts of the Smad2/3 proteins bound to the promoters. These findings reveal novel regulatory mechanisms of Smad2/3-induced transcription and provide an essential resource for understanding their roles.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18955504   Authors: Koinuma D,Tsutsumi S,Kamimura N,Taniguchi H,Miyazawa K,Sunamura M,Imamura T,Miyazono K,Aburatani H
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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Version history 3.1: First introduced

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