SOX9-dependent and -independent transcriptional regulation of human cartilage link protein
SOX9-dependent and -independent transcriptional regulation of human cartilage link protein
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DOI：
10.1074/jbc.m406786200
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发表时间：
2004-12-03
影响因子：
4.8
通讯作者：
Ikegawa, S
中科院分区：
文献类型：
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作者：
Kou, I;Ikegawa, S
软骨连接蛋白是软骨细胞外基质的关键组分。然而，编码软骨连接蛋白（CRTL 1）的基因的转录调节在很大程度上尚不清楚。在这里，我们研究了软骨基质基因和软骨形成的关键调节因子SOX 9对CRTL1的调节。SOX 9的敲除导致CRTL1表达降低。SOX 9在人非软骨细胞永生化细胞系以及间充质干细胞和成人真皮成纤维细胞中有效诱导CRTL1表达。这些结果表明，与其他软骨基质基因一样，SOX 9是CRTL1的关键调节因子。然而，与其他软骨基质基因不同，SOX 9及其已知的转录共激活因子L-SOX 5和SOX 6对CRTL1的激活是细胞类型依赖性的。两个顺式作用增强子元件位于CRTL1的5 '非翻译区。一个包含一个七聚体SOX结合序列，并在几个细胞系中显示SOX 9依赖性增强子活性。另一个显示出细胞类型特异性的SOX 9非依赖性增强子活性。这些发现表明，增强子元件可能介导软骨细胞分化和成熟过程中CRTL1的差异表达。
Cartilage link protein is a key component of the cartilage extracellular matrix. The transcriptional regulation of the gene encoding cartilage link protein (CRTL1) is largely unknown, however. Here, we investigated the regulation of CRTL1 by SOX9, a key regulator of cartilage matrix genes and chondrogenesis. Knockdown of SOX9 resulted in decreased CRTL1 expression. SOX9 induced CRTL1 expression effectively in human nonchondrocytic immortalized cell lines as well as in mesenchymal stem cell and adult dermal fibroblast. These results indicate that, like other cartilage matrix genes, SOX9 is a key regulator of CRTL1. Unlike other cartilage matrix genes, however, the activation of CRTL1 by SOX9 and its known transcriptional co-activators L-SOX5 and SOX6 was cell type-dependent. Two cis-acting enhancer elements resided in the 5'-untranslated region of CRTL1. One contained a heptameric SOX binding sequence and showed SOX9-dependent enhancer activity in several cell lines. The other showed cell type-specific SOX9-independent enhancer activity. These findings suggest that the enhancer elements may mediate differential expression of CRTL1 during chondrocyte differentiation and maturation.