Scleraxis and E47 cooperatively regulate the Sox9-dependent transcription
Scleraxis and E47 cooperatively regulate the Sox9-dependent transcription
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DOI：
10.1016/j.biocel.2009.10.003
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Ozaki, Toshifumi
中科院分区：
文献类型：
--
作者：
Furumatsu, Takayuki;Shukunami, Chisa;Ozaki, Toshifumi
在肌肉骨骼发育过程中，sry型HMG box 9 （Sox9）在间充质凝聚和软骨形成中起着至关重要的作用。另一方面，组织特异性的基本螺旋-环-螺旋（bHLH）转录因子sccleraxis （Scx）调节肌腱和韧带祖细胞的分化。尽管这两种转录因子共同参与细胞谱系的确定，但Sox9和Scx之间的确切相互作用尚不清楚。我们之前已经证明，依赖sox9的转录被染色质上的几个sox9相关分子（如p300和Smad3）协同激活。在这项研究中，我们研究了Scx在sox9依赖性转录中的功能。Sox9和Scx的适当转导刺激了α - 1（II）胶原（Col2a1）基因的表达。在荧光素酶报告基因检测中，Scx及其伴侣E47（与其他bHLH蛋白二聚体）共同增强了sox9依赖性转录。在Scx和E47存在的情况下，Coactivator p300协同提高sox9调控的报告基因的活性，该基因包含Col2a1的启动子和增强子区域。免疫沉淀分析显示Scx和E47与Sox9和p300形成转录复合物。Scx/E47异源二聚体还与染色质上Col2a1启动子的保守E-box序列（CAGGTG）相关。这些发现表明，Scx和E47可能通过与sox9相关的转录复合物结合以及与Col2a1启动子上保守的E-box结合来调节原发性软骨形成。2009爱思唯尔有限公司版权所有。
During musculoskeletal development, Sry-type HMG box 9 (Sox9) has a crucial role in mesenchymal condensation and chondrogenesis. on the other hand, a tissue-specific basic helix-loop-helix (bHLH) transcription factor Scleraxis (Scx) regulates the differentiation of tendon and ligament progenitors. Whereas these two transcription factors cooperatively participate in the determination of cellular lineages, the precise interaction between Sox9 and Scx remains unclear. We have previously demonstrated that the Sox9-dependent transcription is synergistically activated by several Sox9-associating molecules, such as p300 and Smad3, on chromatin. In this study, we investigated the function of Scx in the Sox9-dependent transcription. The expression of alpha 1(II) collagen (Col2a1) gene was stimulated by an appropriate transduction of Sox9 and Scx. Scx and its partner E47, which dimerizes with other bHLH proteins, cooperatively enhanced the Sox9-dependent transcription in luciferase reporter assays. Coactivator p300 synergistically increased the activity of Sox9-regulated reporter gene, which contains promoter and enhancer regions of Col2a1, in the presence of Scx and E47. Immunoprecipitation analyses revealed that Scx and E47 formed a transcriptional complex with Sox9 and p300. Scx/E47 heterodimer also associated with a conserved E-box sequence (CAGGTG) in the Col2a1 promoter on chromatin. These findings suggest that Scx and E47 might modulate the primary chondrogenesis by associating with the Sox9-related transcriptional complex, and by binding to the conserved E-box on Col2a1 promoter. (C) 2009 Elsevier Ltd. All rights reserved.