The basic helix-loop-helix, leucine zipper transcription factor, USF (upstream stimulatory factor), is a key regulator of SF-1 (steroidogenic factor-1) gene expression in pituitary gonadotrope and steroidogenic cells.
Tissue-specific expression of the mammalian FTZ-F1 gene is essential for adrenal and gonadal development and sexual differentiation. The FTZ-F1 gene encodes an orphan nuclear receptor, termed SF-1 (steroidogenic factor-1) or Ad4BP, which is a primary transcriptional regulator of several hormone and steroidogenic enzyme genes that are critical for normal physiological function of the hypothalamic-pituitary-gonadal axis in reproduction. The objective of the current study is to understand the molecular mechanisms underlying transcriptional regulation of SF-1 gene expression in the pituitary. We have studied a series of deletion and point mutations in the SF-1 promoter region for transcriptional activity in alphaT3-1 and L/betaT2 (pituitary gonadotrope), CV-1, JEG-3, and Y1 (adrenocortical) cell lines. Our results indicate that maximal expression of the SF-1 promoter in all cell types requires an E box element at -82/-77. This E box sequence (CACGTG) is identical to the binding element for USF (upstream stimulatory factor), a member of the helix-loop-helix family of transcription factors. Studies of the SF-1 gene E box element using gel mobility shift and antibody supershift assays indicate that USF may be a key transcriptional regulator of SF-1 gene expression.
Harris
A N
AN
Department of Reproductive Medicine, University of California, San Diego, La Jolla 92093-0674, USA.
Mellon
P L
PL
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001692:Biological Transport / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation / Q000502:physiology*; D000882:Haplorhini; D018257:Helix-Loop-Helix Motifs / Q000502:physiology*; D018398:Homeodomain Proteins; D006801:Humans; D007438:Introns; D016350:Leucine Zippers / Q000502:physiology*; D046911:Macromolecular Substances; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D046911:Macromolecular Substances; C515057:NR5A1 protein, human; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; C497182:Usf1 protein, rat; C515058:steroidogenic factor 1, mouse; C515060:steroidogenic factor 1, rat