SOX9 directly regulates the type-II collagen gene

Bell, Donald M., Leung, Keith K. H., Wheatley, Susan C., Ng, Ling Jim, Zhou, Sheila, Ling, Kam Wing, Sham, Mai Har, Koopman, Peter, Tam, Patrick P. L. and Cheah, Kathryn S. E. (1997) SOX9 directly regulates the type-II collagen gene. Nature Genetics, 16 2: 174-178. doi:10.1038/ng0697-174


Author Bell, Donald M.
Leung, Keith K. H.
Wheatley, Susan C.
Ng, Ling Jim
Zhou, Sheila
Ling, Kam Wing
Sham, Mai Har
Koopman, Peter
Tam, Patrick P. L.
Cheah, Kathryn S. E.
Title SOX9 directly regulates the type-II collagen gene
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
1546-1718
Publication date 1997-06
Sub-type Article (original research)
DOI 10.1038/ng0697-174
Volume 16
Issue 2
Start page 174
End page 178
Total pages 5
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Language eng
Abstract 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.
Keyword Sry-Related Gene
Chondrocyte Expression
Activation Domain
Transgenic Mice
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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