Transcription factor Yin Yang 1 (YY1) mediates Prostaglandin F2α (PGF2α) suppression of Steroidogenic Acute Regulatory Protein (StAR) expression via selective promoter site binding in vivo

Abstract

PGF2α plays a pivotal role in ovarian luteolysis by inhibiting the expression of StAR leading to a decrease in intracellular cholesterol transport and luteal steroid production. Previously we have demonstrated in vitro that the transcription factor YY1 binds to three regions in the StAR promoter and that YY1 interacts with the sterol regulatory element binding protein (SREBP) to repress steroid production. This study further defines YY1 interaction with the StAR promoter in vivo. PGF2α consistently suppressed StAR protein and mRNA expression in cultured luteal cells in a dose dependent manner. PGF2α increased YY1 protein levels in a time and dose dependent fashion and YY1 overexpression inhibited both basal and SREBP-induced StAR promoter luciferase activity. Chromatin immuno-precipitation (ChIP) analysis demonstrated that, in contrast to YY1 binding in vitro, YY1 bound specifically to one region of the StAR promoter in vivo. ChIP analysis also demonstrated that SREBP bound to only two of the five StAR promoter sterol response elements identified in vitro. ChIP analysis performed after incubation with PGF2α showed enhanced YY1 binding to the promoter without any alteration in SREBP affinity for its cis-binding region. These data indicate that PGF2α enhances direct YY1/StAR promoter interaction and that YY1 does not inhibit SREBP binding to the StAR promoter in vivo. Supported by NIH HD035163.