STRUCTURE AND LOCALIZATION OF THE HUMAN GENE ENCODING SR-BI CLA-1 - EVIDENCE FOR TRANSCRIPTIONAL CONTROL BY STEROIDOGENIC FACTOR-1/

The scavenger receptor, class B, type 1 receptor (SR-BI) mediates the selective transport of lipids from high density lipoprotein to cells. We describe the structure and subchromosomal location of human SR-BI a nd provide evidence that it is regulated by the transcription factor, steroidogenic factor 1 (SF-1). SR-BI resides on chromosome 12q24.2-qte r, spans similar to 75 kilobase pairs, and contains 13 exons. RNA blot analysis of human tissues reveals an expression pattern similar to th at described previously for rodents with the highest levels of mRNA in the adrenal gland, ovary, and liver. Unlike rodents, human SR-BI was expressed at high levels in the placenta. The transcription start site for SR-BI was mapped, and DNA sequence analysis revealed a binding si te for SF-1 in the proximal 5'-flanking sequence. SF-1, an orphan memb er of the nuclear hormone receptor gene family, plays a key role in th e regulation of steroidogenesis and is expressed at high levels in ste roidogenic tissues. SF-1 binds to the SR-BI promoter in a sequence-spe cific manner, and efficient transcription from this promoter in adreno cortical Y1 cells is dependent on an intact SF-1 site. These data exte nd our understanding of SF-1 function within steroidogenic tissues and suggest that SR-BI, which serves to supply selected tissues with lipo protein-derived lipids, is part of the repertoire of SF-1-responsive g enes involved in steroidogenesis.