The transcription factor Znf219 regulates chondrocyte differentiation by assembling a transcription factory with Sox9
The transcription factor Znf219 regulates chondrocyte differentiation by assembling a transcription factory with Sox9
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DOI：
10.1242/jcs.071373
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发表时间：
2010-11
影响因子：
4
通讯作者：
Yoko Takigawa;K. Hata;S. Muramatsu;K. Amano;K. Ono;M. Wakabayashi;A. Matsuda;K. Takada;R. Nishimura;T. Yoneda
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文献类型：
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作者：
Yoko Takigawa;K. Hata;S. Muramatsu;K. Amano;K. Ono;M. Wakabayashi;A. Matsuda;K. Takada;R. Nishimura;T. Yoneda
Sox 9是软骨形成的重要转录因子，通过调控软骨形成基因的表达。然而，其调控机制并不完全清楚。为了解决这个问题，我们试图通过使用胶原2α1（Col2α1）基因启动子融合荧光素酶报告基因筛选软骨细胞系ATDC 5的cDNA文库来鉴定Sox 9的转录伴侣。其中一个阳性克隆编码Znf219基因。原位杂交结果表明，Znf219 mRNA在肢芽中特异表达，其中Col2α1和Sox 9在肢芽中表达较强。Znf219显著增强Sox 9在Col2a1基因启动子上的转录活性。此外，Znf219与Sox 9物理相关，并与Sox 9共定位于细胞核中。我们还发现，Znf219的过度表达大大增加了Sox9诱导的Col2a1，聚集蛋白聚糖和Col11a2的mRNA表达。因此，Znf219的敲低降低了Sox9诱导的这些基因的mRNA表达。此外，显性负突变体Znf219抑制Bmp2诱导的软骨细胞分化。我们的研究结果表明，Znf219作为Sox 9的转录伴侣在软骨细胞分化的调节中起着重要的作用。
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.