Cell-Specific Polymorphism and Hormonal Regulation of DNA Methylation in Scavenger Receptor Class B, Type I

Abstract

The scavenger receptor class B, type I (SR-BI), is a cell-surface glycoprotein that mediates selective uptake of high density lipoprotein (HDL)-derived cholesteryl ester. SR-BI plays an important role in cellular delivery of cholesterol. Both human and rodent SR-BI are expressed most abundantly in the liver parenchymal cells and steroidogenic cells of the adrenal gland and gonads, where the selective pathway exhibits its highest activity. In steroidogenic cells, the expression of SR-BI is regulated by trophic hormones (adrenocorticotropic hormone or gonadotropins luteinizing hormone or follicle-stimulating hormone) in concert with the regulation of steroid hormone production. DNA methylation has been implicated in a large number of biological processes mainly by regulating gene expression. The SR-BI promoter contains one CpG island (CGI) in its promoter and seven CGIs in its intronic regions. Here, we studied the DNA methylation status of SR-BI gene and provide evidence that the DNA methylation is cell specific in this gene promoter as well as in intronic regions. The DNA methylation in the SR-BI promoter is subject to N(6), 2'-O-dibutyryladenosine3':5'-cyclic monophosphate regulation in mouse adrenal Y1 cells and mouse Leydig tumor cells (MLTCs). The seven intron CGIs are methylated differentially in Y1 cells, MLTCs, ovarian granulosa cells, and mouse liver hepa 1-6 cells. Our experiments raised the possibility that DNA methylation participates in hormonal regulation of SR-BI expression in a tissue-specific manner. We further suggest that the cell-specific DNA methylation in SR-BI intronic regions may be associated with specific biological function(s) of these regions, including regulation of gene expression.