The transcription factor Znf219 regulates chondrocyte differentiation by assembling a transcription factory with Sox9

Yoko Takigawa, Kenji Hata, Shuji Muramatsu, Katsuhiko Amano, Koichiro Ono, Makoto Wakabayashi, Akio Matsuda, Kenji Takada, Riko Nishimura, Toshiyuki Yoneda

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

Sox9 is an essential transcription factor for chondrogenesis by regulating the expression of chondrogenic genes. However, its regulatory mechanism is not fully understood. To address this, we attempted to identify the transcriptional partners of Sox9 by screening the cDNA library of the chondrogenic cell line ATDC5 using the collagen 2α1 (Col2α1) gene promoter fused to a luciferase reporter gene. One of the positive clones encoded the Znf219 gene. Whole mount in situ hybridization experiments indicated that Znf219 mRNA was specifically expressed in the developing limb buds where Col2α1 and Sox9 were strongly expressed. Znf219 markedly enhanced the transcriptional activity of Sox9 on the Col2a1 gene promoter. In addition, Znf219 is physically associated with Sox9 and is colocalized with Sox9 in the nucleus. We also found that overexpression of Znf219 profoundly increased Sox9-induced mRNA expression of Col2a1, aggrecan and Col11a2. Consistently, knockdown of Znf219 decreased the Sox9-induced mRNA expression of these genes. Furthermore, a dominant-negative mutant Znf219 inhibited Bmp2-induced chondrocyte differentiation. Our results suggest that Znf219 plays an important role in the regulation of chondrocyte differentiation as a transcriptional partner of Sox9.

Original languageEnglish
Pages (from-to)3780-3788
Number of pages9
JournalJournal of cell science
Volume123
Issue number21
DOIs
Publication statusPublished - Nov 1 2010
Externally publishedYes

Keywords

  • Chondrogenesis
  • Sox9
  • Transcription factor

ASJC Scopus subject areas

  • Cell Biology

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