Document Detail

SOX9 directly regulates the type-II collagen gene.
MedLine Citation:
PMID:  9171829     Owner:  NLM     Status:  MEDLINE    
Mutations in human SOX9 are associated with campomelic dysplasia (CD), characterised by skeletal malformation and XY sex reversal. During chondrogenesis in the mouse, Sox9 is co-expressed with Col2a1, the gene encoding type-II collagen, the major cartilage matrix protein. Col2a1 is therefore a candidate regulatory target of SOX9. Regulatory sequences required for chondrocyte-specific expression of the type-II collagen gene have been localized to conserved sequences in the first intron in rats, mice and humans. We show here that SOX9 protein binds specifically to sequences in the first intron of human COL2A1. Mutation of these sequences abolishes SOX9 binding and chondrocyte-specific expression of a COL2A1-driven reporter gene (COL2A1-lacZ) in transgenic mice. Furthermore, ectopic expression of Sox9 trans-activates both a COL2A1-driven reporter gene and the endogenous Col2a1 gene in transgenic mice. These results demonstrate that COL2A1 expression is directly regulated by SOX9 protein in vivo and implicate abnormal regulation of COL2A1 during, chondrogenesis as a cause of the skeletal abnormalities associated with campomelic dysplasia.
D M Bell; K K Leung; S C Wheatley; L J Ng; S Zhou; K W Ling; M H Sham; P Koopman; P P Tam; K S Cheah
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature genetics     Volume:  16     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  1997 Jun 
Date Detail:
Created Date:  1997-06-18     Completed Date:  1997-06-18     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  174-8     Citation Subset:  IM    
Department of Biochemistry, University of Hong Kong, Hong Kong.
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MeSH Terms
Base Sequence
Cartilage / embryology
Collagen / genetics*
Gene Expression Regulation, Developmental / physiology*
High Mobility Group Proteins / physiology*
Mice, Transgenic
Molecular Sequence Data
SOX9 Transcription Factor
Transcription Factors / physiology*
Reg. No./Substance:
0/High Mobility Group Proteins; 0/SOX9 Transcription Factor; 0/SOX9 protein, human; 0/Sox9 protein, mouse; 0/Transcription Factors; 9007-34-5/Collagen
Comment In:
Nat Genet. 1997 Jun;16(2):114-5   [PMID:  9171818 ]

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