| Mouse Snail family transcription repressors regulate chondrocyte, extracellular matrix, type II collagen, and aggrecan. | |
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MedLine Citation:
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PMID: 12917416 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Snail family genes are conserved among species during evolution and encode transcription factors expressed at different stages of development in different tissues. These genes are involved in a broad spectrum of biological functions: cell differentiation, cell motility, cell cycle regulation, and apoptosis. However, little is known about the target genes involved in these functions. Here we show that mouse Snail family members, Snail (Sna) and Slug (Slugh), are involved in chondrocyte differentiation by controlling the expression of type II collagen (Col2a1) and aggrecan. In situ hybridization analysis of developing mouse limb demonstrated that Snail and Slug mRNAs were highly expressed in hypertrophic chondrocytes. Inversely, the expression of collagen type II mRNA disappeared during hypertrophic differentiation. Snail and Slug mRNA expression was down-regulated during differentiation of the mouse chondrogenic cell line ATDC5 and overexpression of exogenous Snail or Slug in ATDC5 cells inhibited expression of collagen type II and aggrecan mRNA. Reporter analysis revealed Snail and Slug suppressed the promoter activity of Col2a1, and the E-boxes in the promoter region were the responsible element. Gel shift assay demonstrated the binding of Snail to the E-box. Because type II collagen and aggrecan are major functional components of extracellular matrix in cartilage, these results suggest an important role for Snail-related transcription repressors during chondrocyte differentiation. |
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Authors:
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Kenji Seki; Toshihiko Fujimori; Pierre Savagner; Akiko Hata; Tomonao Aikawa; Naoshi Ogata; Yoichi Nabeshima; Lee Kaechoong |
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Publication Detail:
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Type: Journal Article Date: 2003-08-12 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 278 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2003 Oct |
Date Detail:
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Created Date: 2003-10-20 Completed Date: 2004-01-05 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 41862-70 Citation Subset: IM |
Affiliation:
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Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA. kseki@anat1.med.kyoto-u.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aggrecans Animals Cell Differentiation / genetics Cell Line Chondrocytes / cytology*, metabolism Collagen Type II / genetics* DNA-Binding Proteins / physiology* E-Box Elements Embryo, Mammalian Extracellular Matrix Extracellular Matrix Proteins* Gene Expression Regulation, Developmental Lectins, C-Type Mice Promoter Regions, Genetic Proteoglycans RNA, Messenger / analysis Repressor Proteins / physiology Tibia Transcription Factors / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Agc1 protein, mouse; 0/Aggrecans; 0/Collagen Type II; 0/DNA-Binding Proteins; 0/Extracellular Matrix Proteins; 0/Lectins, C-Type; 0/Proteoglycans; 0/RNA, Messenger; 0/Repressor Proteins; 0/Transcription Factors; 0/snail family transcription factors |
| Comments/Corrections | |
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