Multiple modes of repression by the Smad transcriptional corepressor TGIF Journal Article


Authors: Wotton, D.; Lo, R. S.; Swaby, L. A. C.; Massagué, J.
Article Title: Multiple modes of repression by the Smad transcriptional corepressor TGIF
Abstract: TGIF is a DNA-binding homeodomain protein that has been demonstrated to play a role in transforming growth factor β-regulated transcription and implicated in the control of retinoid-responsive transcription. We investigated the intrinsic transcriptional activity of TGIF fused to a heterologous DNA-binding domain. Our results demonstrate that TGIF is a transcriptional repressor able to repress transcription from several different promoters. Repression by TGIF is insensitive to the distance at which it is bound from the promoter. Moreover, the wild type TGIF effectively represses transcription when bound to its cognate DNA-binding site via its homeodomain. Deletion analysis revealed the presence of at least two separable repression domains within TGIF. Repression by one of these is dependent on the activity of histone deacetylases (HDACs), whereas the other appears not to require HDAC activity. Finally, we demonstrate that TGIF interacts with HDACs via its carboxyl-terminal repression domain. Together, these results suggest that TGIF is a multifunctional transcriptional repressor, which acts in part by recruiting HDAC activity.
Keywords: controlled study; nonhuman; animal cell; animals; transforming growth factor beta; homeodomain proteins; transcription, genetic; enzyme activity; structure-activity relationship; cos cells; animalia; dna; transcription regulation; immunoprecipitation; immunoblotting; binding site; homeodomain protein; dna binding; monkey; repressor proteins; histone deacetylases; retinoid; histone deacetylase; mink; priority journal; article; mustela vison
Journal Title: Journal of Biological Chemistry
Volume: 274
Issue: 52
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 1999-12-24
Start Page: 37105
End Page: 37110
Language: English
DOI: 10.1074/jbc.274.52.37105
PUBMED: 10601270
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 16 August 2016 -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. David Wotton
    7 Wotton
  2. Joan Massague
    388 Massague
  3. Laurie-Anne C Swaby
    1 Swaby