Smad3 activates the Sox9-dependent transcription on chromatin

被引：77

作者：

Furumatsu, Takayuki ^{[1
,2
]}

Ozaki, Toshifumi ^{[1
]}

Asahara, Hiroshi ^{[2
,3
]}

机构：

[1] Okayama Univ, Grad Sch, Dept Orthopaed Surg, Okayama 7008558, Japan

[2] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA

[3] Natl Ctr Child Hlth & Dev, Tokyo 1578535, Japan

来源：

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | 2009年 / 41卷 / 05期

基金：

日本学术振兴会;

关键词：

Chondrogenesis; Chromatin; p300; Smad3; Sox9; NUCLEOSOME ASSEMBLY PROTEIN-1; MESENCHYMAL STEM-CELLS; GENE-EXPRESSION; REGULATES CHONDROGENESIS; II COLLAGEN; SOX9; P300; DIFFERENTIATION; COACTIVATORS; KINASE;

D O I：

10.1016/j.biocel.2008.10.032

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Transforming growth factor (TGF)-beta 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-beta-regulated Smad3 induces chondrogenesis through the activation of Sox9-dependent transcription. However, the cross-talk between TGF-beta 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-beta-dependent manner. Recombinant Sox9 associated with phosphorylated Smad3/4 and recognized the enhancer region of type 11 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-beta signal Smad3 plays a key role for chromatin remodeling to induce chondrogenesis via its association with Sox9. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1198 / 1204

页数：7

共 42 条

[1]

The transcrintion factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6 [J].