Loss of transcriptional repression of three sterol-regulated genes in mutant hamster cells

摘要: Two genes that encode enzymes in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and HMG-CoA synthase, the gene encoding low density lipoprotein (LDL) receptor are repressed when sterols accumulate animal cells. Their 5'-flanking regions contain a common element, designated sterol regulatory element-1 (SRE-1). In synthase LDL promoters, SRE-1 enhances transcription absence of is inactivated presence sterols. promoter, region containing represses present. current studies, we show retains enhancer function but loses sensitivity mutant Chinese hamster ovary cells resistant to repressor, 25-hydroxycholesterol. sterols, produced high levels all three sterol-regulated mRNAs, there was no repression by When transfected with plasmids each regulated promoters fused bacterial reporter gene, showed significant mutated prior transfection into cells, markedly reduced. Thus, 25-hydroxycholesterol-resistant retain protein binding they have lost abolishes this enhancement Mutation 30-base pair segment promoter contains did not reduce indicating driven elements other than SRE-1. Nevertheless, failed be These data suggest factor mediates effects on has been functionally