Functions of the upstream and proximal steroidogenic factor 1 (SF-1)-binding sites in the CYP11A1 promoter in basal transcription and hormonal response
Mc. Hu et al., Functions of the upstream and proximal steroidogenic factor 1 (SF-1)-binding sites in the CYP11A1 promoter in basal transcription and hormonal response, MOL ENDOCR, 15(5), 2001, pp. 812-818
The CYP11A1 gene encodes P450scc (cholesterol side-chain cleavage enzyme),
which catalyzes the first step for the synthesis of steroids. Expression of
CYP11A1 is controlled by transcription factor SF-1 (steroidogenic factor 1
). Two functional SF-1-binding sites, P and U, located at -40 and -1,600 re
gions of the CYP11A1 gene, have been identified, but their exact functions
with respect to basal activation vs, cAMP response have not been dissected.
We have addressed this question by examining the ability of the mutated hu
man CYP11A1 promoter to drive LacZ reporter gene expression in transgenic m
ouse lines. The activity of the mtP mutant promoter was greatly reduced, in
dicating the importance of the P site. Mutation of the upstream U site also
resulted in reduced reporter gene expression, but some residual activity r
emained. This residual reporter gene activity was detected in the adrenal a
nd gonad in a tissue-specific manner. ACTH and hCG can stimulate LacZ gene
expression in the adrenals and testes of transgenic mice driven by the wild
-type but not the mtU promoter, These results indicate that the upstream SF
-1-binding site is required for hormonal stimulation. Our experiments demon
strate the participation of both the proximal and the upstream SF-1-binding
sites in hormone-responsive transcription.