SnoN co-repressor binds and represses smad7 gene promoter.
SnoN and Ski oncoproteins are co-repressors for Smad proteins and repress TGF-beta-responsive gene expression. The smad7 gene is a TGF-beta target induced by Smad signaling, and its promoter contains the Smad-binding element (SBE) required for a positive regulation by the TGF-beta/Smad pathway. SnoN and Ski co-repressors also bind SBE but regulate negatively smad7 gene. Ski along with Smad4 binds and represses the smad7 promoter, whereas the repression mechanism by SnoN is not clear. Ski and SnoN overexpression inhibits smad7 reporter expression induced through TGF-beta signaling. Using chromatin immunoprecipitation assays, we found that SnoN binds smad7 promoter at the basal condition, whereas after a short TGF-beta treatment for 15-30 min SnoN is downregulated and no longer bound smad7 promoter. Interestingly, after a prolonged TGF-beta treatment SnoN is upregulated and returns to its position on the smad7 promoter, functioning probably as a negative feedback control. Thus, SnoN also seems to regulate negatively the TGF-beta-responsive smad7 gene by binding and repressing its promoter in a similar way to Ski.
Briones-Orta
Marco A
MA
Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico.
Sosa-Garrocho
Marcela
M
Moreno-Alvarez
Paola
P
Fonseca-Sánchez
Miguel A
MA
Macías-Silva
Marina
M
D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D051906:Smad7 Protein / Q000235:genetics*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C060615:SKIL protein, human; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta