Human Molecular Genetics, Vol 8, 691-696, Copyright © 1999 by Oxford University Press
Y Kanai and P Koopman
Mutations in SOX9 cause campomelic dysplasia (CD), a dominant skeletal
dysmorphology and XY sex reversal syndrome. The CD phenotype is sensitive
to dosage and expression levels of SOX9. Sox9 is expressed during
chondrocyte differentiation and is up-regulated in male and down- regulated
in female genital ridges during sex differentiation. In order to study the
sex- and tissue-specific regulation of Sox9, we have defined the
transcription start site and characterized the mouse Sox9 promoter region.
The Sox9 proximal promoter shows moderately high nucleotide similarity
between mouse and human. Transient transfection experiments using various
deletion constructs of the 6.8 kb upstream region of mouse Sox9 fused to a
luciferase reporter showed that the interval between 193 and 73 bp from the
transcription start site is essential for maximal promoter activity in cell
lines and in primary male and female gonadal somatic cells and liver cells
isolated from 13.5 d.p.c. mouse embryos. This minimal promoter region was
shown by DNase I hypersensitive site assay to be in an 'open' state of
chromatin structure in gonads of both sexes, but not in the liver. Promoter
activity was higher in testis than in ovary and liver, but deletion of the
region from -193 to -73 bp abolished this difference. We conclude that the
proximal promoter region is in part responsible for the sex- and
tissue-specific expression of the Sox9 gene and that more distal positive
and negative elements contribute to its regulation in vivo, consistent with
the observation that translocations upstream from SOX9 can result in
campomelic dysplasia.
ARTICLES
Structural and functional characterization of the mouse Sox9 promoter: implications for campomelic dysplasia
Centre for Molecular and Cellular Biology, The University of Queensland, Brisbane, Queensland 4072, Australia.
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