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Repression of the Steroidogenic Acute Regulatory Gene by the Multifunctional Transcription Factor Yin Yang 1

Departments of Obstetrics and Gynecology (A.C.N., W.S.-E., D.L., M.P.M.) and Biochemistry and Molecular Biology (M.P.M.), University of South Florida, Tampa, Florida 33606

Address all correspondence and requests for reprints to: Mark P. McLean, Ph.D., Department of Obstetrics and Gynecology, University of South Florida, Harbourside Medical Tower, Suite 529, 4 Columbia Drive, Tampa, Florida 33606. E-mail: . mmclean{at}hsc.usf.edu

The transport of cholesterol to the inner mitochondrial membrane by the steroidogenic acute regulatory (StAR) protein is a critical step in steroidogenesis. The current study was designed to examine whether the multifunctional transcription factor Yin Yang 1 (YY1) was able to repress activation of the StAR gene. YY1 bound to three putative YY1-binding sites in the rat StAR promoter. Cotransfection of the StAR promoter linked to a luciferase reporter gene and YY1 in the presence or absence of sterol regulatory element binding protein-1a (SREBP-1a) resulted in transcriptional repression. YY1 was found to colocalize in the nucleus with SREPB-1a. YY1 inhibited SREBP-1a/nuclear factor Y (NF-Y) enhancement of StAR activation and YY1 decreased SREBP-1a binding to a sterol regulatory element in the presence or absence of NF-Y. YY1 also decreased NF-Y binding to a nonconsensus NF-Y-binding motif in the StAR promoter. These studies provide novel information on the mechanisms of YY1-mediated repression of the StAR gene.

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