Orphan receptor chicken ovalbumin upstream promoter transcription factors inhibit steroid factor-1, upstream stimulatory factor, and activator protein-1 activation of ovine follicle-stimulating hormone receptor expression via composite cis-elements.
The FSH receptor (FSHR) is selectively expressed in the granulosa and Sertoli cells in a development-dependent manner. Little is known regarding how the regulatory factors balance expression of this gene in ovarian cycles or spermatogenic stages. We have used the ovine FSHR promoter as a model system and identified a third regulatory element (RE-3) located at -197 to -171 of the strongest promoter. Gel mobility shift and antibody supershift assays demonstrated that nuclear factors c-Fos/c-Jun, steroidogenic factor-1 (SF-1), upstream stimulatory factor-1/2 (USF-1/2), and chicken ovalbumin upstream promoter transcription factor-1/2 (COUP-TFI/II) potentially bound to RE-3. We have also extended our previous observations by showing that a sequence containing an E-box was not only bound by USF proteins but also recognized by COUP-TF orphan receptors. Functional studies demonstrated that USF-1/2, c-Fos/c-Jun, and SF-1 were activators, whereas COUP-TFs were repressors. Our studies indicated that RE-3 mediated SF-1 activation as well as phorbol 12-myristate 13-acetate stimulation, whereas COUP-TFs inhibited AP-1, USFs, and SF-1 activation. We also demonstrated that both COUP-TF-binding sites in the core promoter were required for the bipartite elements to oppose their competitor binding. These data suggest a mechanism by which positive and negative regulators compete for the common regulatory elements, providing antagonistic pathways that might govern the expression of FSHR in gonadal cells.
Xing
Weirong
W
Molecular Reproduction Research Laboratory, Clinical Research Institute of Montreal, Montreal, Quebec, Canada H2W 1R7.
Danilovich
Natalia
N
Sairam
M Ram
MR
D000818:Animals; D001665:Binding Sites; D051838:COUP Transcription Factor I; D051836:COUP Transcription Factors; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D015870:Gene Expression / Q000187:drug effects; D006107:Granulosa Cells; D018398:Homeodomain Proteins; D007150:Immunohistochemistry; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear; D011962:Receptors, FSH / Q000235:genetics*; D011987:Receptors, Steroid; D012045:Regulatory Sequences, Nucleic Acid; D012756:Sheep; D054339:Steroidogenic Factor 1; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D014162:Transfection; D051720:Upstream Stimulatory Factors
D051838:COUP Transcription Factor I; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C497590:Nr2f1 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D011962:Receptors, FSH; D011987:Receptors, Steroid; D054339:Steroidogenic Factor 1; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; C515058:steroidogenic factor 1, mouse; D004247:DNA; D013755:Tetradecanoylphorbol Acetate