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| SOX9 directly regulates the type-II collagen gene |
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| Author(s): Bell DM, Leung KKH, Wheatley SC, Ng LJ, Zhou S, Ling KW, Sham MH, Koopman P, Tam PPL, Cheah KSE |
| Source: NATURE GENETICS Volume: 16 Issue: 2 Pages: 174-178 Published: JUN 1997 |
| Times Cited: 341 References: 30 |
| Abstract: Mutations in human SOX9 are associated with campomelic dysplasia (CD), characterised by skeletal malformation and XY sex reversal(1-3). During chondrogenesis in the mouse, Sox9 is coexpressed with Col2a1, the gene encoding type-II collagen, the major cartilage matrix protein(4). 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(5-8). 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV HONG KONG, DEPT BIOCHEM, HONG KONG, HONG KONG
2. UNIV QUEENSLAND, CTR CELLULAR & MOL BIOL, BRISBANE, QLD 4072 AUSTRALIA
3. UNIV QUEENSLAND, DEPT ANAT SCI, BRISBANE, QLD 4072 AUSTRALIA
4. CHILDRENS MED RES INST, WENTWORTHVILLE 2145, AUSTRALIA |
| Publisher: NATURE PUBLISHING CO, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 |
| Subject Category: Genetics & Heredity |
| IDS Number: XB543 |
| ISSN: 1061-4036 |
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