RRC ID 38175
著者 Takigawa Y, Hata K, Muramatsu S, Amano K, Ono K, Wakabayashi M, Matsuda A, Takada K, Nishimura R, Yoneda T.
タイトル The transcription factor Znf219 regulates chondrocyte differentiation by assembling a transcription factory with Sox9.
ジャーナル J Cell Sci
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.
巻・号 123(Pt 21)
ページ 3780-8
公開日 2010-11-1
DOI 10.1242/jcs.071373
PII jcs.071373
PMID 20940257
MeSH Animals Bone Morphogenetic Protein 2 / metabolism Cell Differentiation / genetics Cell Line Cell Nucleus / metabolism* Chondrocytes / metabolism* Chondrocytes / pathology DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Extremities / growth & development Gene Library Genetic Testing Humans Mice Mutation / genetics Protein Binding SOX9 Transcription Factor / genetics SOX9 Transcription Factor / metabolism* Transcription Factors / genetics Transcription Factors / metabolism* Transcriptional Activation
IF 4.573
引用数 31
WOS 分野 CELL BIOLOGY
リソース情報
ヒト・動物細胞 10T1/2(RCB0247) ATDC5(RCB0565) C2C12(RCB0987) CHO-K1(RCB0285) COS-7(RCB0539)