Short communication: Identification of the bovine sterol regulatory element binding protein-1c promoter and its activation by liver X receptor1

Sterol regulatory element binding proteins (SREBP) are a family of transcription factors that regulate cholesterogenesis and lipogenesis. Sterol regulatory element binding proteins-1a and -1c are transcribed from the same gene by the use of alternate promoters, and only differ at their first exon. Sterol regulatory element binding protein-1c is hypothesized to be an important regulator of genes involved in milk fat synthesis in the lactating dairy cow. However, the bovine SREBP-1c promoter has not been previously characterized, and studies to date that have investigated the role of SREBP-1 in the bovine mammary gland have not distinguished between isoforms 1a and 1c. The purpose of this study was to characterize the bovine SREBP-1c promoter and to investigate the DNA elements involved in the regulation of SREBP-1c expression by the liver X receptor agonist T0901317 in 2 different bovine mammary epithelial cell lines. Luciferase reporter constructs containing the wild-type SREBP-1c promoter or constructs with mutated liver X receptor response elements or sterol response element were transfected into MacT cells and bovine mammary epithelial (BME-UV) cells. We have demonstrated that the liver X receptor response elements sites in the SREBP-1c promoter are necessary for mediating the T0901317 response, and that stimulation through the sterol response element site plays only a minor role in this pathway. This report describes the bovine SREBP-1c promoter and its regulation by liver X receptor in bovine mammary epithelial cells.