The Smad transcriptional corepressor TGIF recruits mSin3

D. Wotton, Paul S Knoepfler, C. D. Laherty, R. N. Eisenman, J. Massagué

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


The homeodomain protein TG-interacting factor (TGIF) represses transcription by histone deacetylase-dependent and -independent means. Heterozygous mutations in human TGIF result in holoprosencephaly, a severe genetic disorder affecting craniofacial development, suggesting that TGIF is critical for normal development. After transforming growth factorβ (TGFβ) stimulation, Smad proteins enter the nucleus and form transcriptional activation complexes or interact with TGIF, which functions as a corepressor. The relative levels of Smad corepressors and coactivators present within the cell may determine the outcome of a TGFβ response. We show that TGIF interacts directly with the paired amphipathic α-helix 2 domain of the mSin3 corepressor, and TGIF recruits mSin3 to a TGFβ-activated Smad complex. The mSin3 interaction domain of TGIF has been shown to be essential for repression of a TGFβ transcriptional response. Thus, TGIF represents a targeting component of the mSin3 corepressor complex.

Original languageEnglish (US)
Pages (from-to)457-463
Number of pages7
JournalCell Growth and Differentiation
Issue number9
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology


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