Smad3 activates the Sox9-dependent transcription on chromatin.
Smad3 activates the Sox9-dependent transcription on chromatin.
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DOI：
10.1016/j.biocel.2008.10.032
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发表时间：
2009-05
影响因子：
4
通讯作者：
Asahara, Hiroshi
中科院分区：
文献类型：
--
作者：
Furumatsu, Takayuki;Ozaki, Toshifumi;Asahara, Hiroshi
转化生长因子（TGF）-β在Sry型高迁移率族蛋白盒（Sox）调控的软骨形成中发挥重要作用。软骨发生分化也受染色质介导的转录控制。我们以前报道过TGF-β调节的Smad 3通过激活Sox 9依赖的转录诱导软骨形成。然而，TGF-β信号和Sox 9对染色质介导的转录之间的串扰尚未阐明。在本研究中，我们研究了活性的Smad 3，Sox 9，和辅激活因子p300使用体外染色质组装模型。荧光素酶报告基因检测显示Smad 3以TGF-β依赖的方式刺激Sox 9介导的转录。重组Sox 9与磷酸化Smad 3/4结合，识别II型胶原基因的增强子区域。体外转录和S1核酸酶分析表明，Smad 3和p300协同激活Sox 9依赖的染色质模板转录。磷酸化Smad 3、Sox 9和p300的联合处理对于染色质介导的转录的激活是必要的。这些发现表明TGF-β信号Smad 3通过与Sox 9的结合在染色质重塑诱导软骨形成中起关键作用。
Transforming growth factor (TGF)-β has an essential role for the Sry-type high-mobility-group box (Sox)-regulated chondrogenesis. Chondrogenic differentiation is also controlled by chromatin-mediated transcription. We have previously reported that TGF-β-regulated Smad3 induces chondrogenesis through the activation of Sox9-dependent transcription. However, the cross-talk between TGF-β signal and Sox9 on chromatin-mediated transcription has not been elucidated. In the present study, we investigated the activity of Smad3, Sox9, and coactivator p300 using an in vitro chromatin assembly model. Luciferase reporter assays revealed that Smad3 stimulated the Sox9-mediated transcription in a TGF-β-dependent manner. Recombinant Sox9 associated with phosphorylated Smad3/4 and recognized the enhancer region of type II collagen gene. In vitro transcription and S1 nuclease assays showed that Smad3 and p300 cooperatively activated the Sox9-dependent transcription on chromatin template. The combination treatment of phosphorylated Smad3, Sox9, and p300 were necessary for the activation of chromatin-mediated transcription. These findings suggest that TGF-β signal Smad3 plays a key role for chromatin remodeling to induce chondrogenesis via its association with Sox9.
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影响因子：
64.5
作者：
Kitagawa, H;Fujiki, R;Kato, S
通讯作者：
Kato, S
DOI：
10.1073/pnas.0407510102
发表时间：
2005-02-15
影响因子：
11.1
作者：
Kawakami, Y;Tsuda, M;Asahara, H
通讯作者：
Asahara, H
影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
5.3
作者：
Asahara, H;Tartare-Deckert, S;Montminy, M
通讯作者：
Montminy, M
影响因子：
64.8
作者：
Felsenfeld, G;Groudine, M
通讯作者：
Groudine, M