Basic helix-loop-helix transcription factor Twist1 inhibits transactivator function of master chondrogenic regulator Sox9

Shoujun Gu, Thomas G. Boyer, Michael C. Naski

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Canonical Wnt signaling strongly inhibits chondrogenesis. Previously, we identified Twist1 as a critical downstream mediator of Wnt in repression of chondrocyte differentiation. However, the mechanistic basis for the antichondrogenic activity of Twist1 has not heretofore been established. Here, we show that Twist1 suppresses cartilage development by directly inhibiting the transcriptional activity of Sox9, the master regulator of chondrogenesis. Twist1, through its carboxyl-terminal Twist-box, binds to the Sox9 high mobility group DNA-binding domain, inhibiting Sox9 transactivation potential. In chondrocyte precursor cells, Twist1, in a Twist-box-dependent manner, inhibits Sox9-dependent activation of chondrocyte marker gene expression by blocking Sox9-enhancer DNA association. These findings identify Twist1 as an inhibitor of Sox9 and further suggest that the balance between Twist1 and Sox9 may determine the earliest steps of chondrogenesis.

Original languageEnglish (US)
Pages (from-to)21082-21092
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number25
DOIs
StatePublished - Jun 15 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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