期刊
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
卷 41, 期 5, 页码 1198-1204出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2008.10.032
关键词
Chondrogenesis; Chromatin; p300; Smad3; Sox9
资金
- Department of Molecular and Experimental Medicine
- NIH [AR50631]
- JST SORST Genome Network Project (MEXT)
- Grants-in Aid for Scientific Research (MEXT)
- Research on Child Health and Development, Research on Publicly, Essential Drugs and Medical Device (Japan Health Sciences Foundation)
- Japan Society for the Promotion of Science [18890115, 20791040]
- Japanese Foundation for Research and Promotion of Endoscopy
- Uehara Memorial Foundation
- Grants-in-Aid for Scientific Research [18890115] Funding Source: KAKEN
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据