Linked Life Data

2570073

Source:http://linkedlifedata.com/resource/pubmed/id/2570073

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
1989-10-12
pubmed:abstractText
Two genes that encode enzymes in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and HMG-CoA synthase, and the gene encoding the low density lipoprotein (LDL) receptor are repressed when sterols accumulate in animal cells. Their 5'-flanking regions contain a common element, designated sterol regulatory element-1 (SRE-1). In the HMG-CoA synthase and LDL receptor promoters, the SRE-1 enhances transcription in the absence of sterols and is inactivated in the presence of sterols. In the HMG-CoA reductase promoter, the region containing the SRE-1 represses transcription when sterols are present. In the current studies, we show that the SRE-1 retains enhancer function but loses sterol sensitivity in mutant Chinese hamster ovary cells that are resistant to the repressor, 25-hydroxycholesterol. In the absence of sterols, the mutant cells produced high levels of all three sterol-regulated mRNAs, and there was no repression by 25-hydroxycholesterol. When transfected with plasmids containing each of the regulated promoters fused to a bacterial reporter gene, the mutant cells showed high levels of transcription in the absence of sterols and no significant repression by sterols. When the SRE-1 in the LDL receptor and HMG-CoA synthase promoters was mutated prior to transfection into the mutant cells, transcription was markedly reduced. Thus, the 25-hydroxycholesterol-resistant cells retain a protein that enhances transcription by binding to the SRE-1 in the absence of sterols, but they have lost the function of a protein that abolishes this enhancement in the presence of sterols. Mutation of a 30-base pair segment of the HMG-CoA reductase promoter that contains the SRE-1 did not reduce transcription in the mutant cells, indicating that this promoter is driven by elements other than the SRE-1. Nevertheless, this promoter failed to be repressed by sterols in the mutant cells. These data suggest that a common factor mediates the effects of sterols on the SRE-1 in all three promoters and that this factor has been functionally lost in the 25-hydroxycholesterol-resistant cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
264
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15634-41
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:2570073-Amphotericin B, pubmed-meshheading:2570073-Animals, pubmed-meshheading:2570073-Cell Line, pubmed-meshheading:2570073-Cell Survival, pubmed-meshheading:2570073-Cholesterol, pubmed-meshheading:2570073-Cricetinae, pubmed-meshheading:2570073-Cricetulus, pubmed-meshheading:2570073-Drug Resistance, pubmed-meshheading:2570073-Enzyme Repression, pubmed-meshheading:2570073-Female, pubmed-meshheading:2570073-Gene Expression Regulation, pubmed-meshheading:2570073-Genes, pubmed-meshheading:2570073-Hydroxycholesterols, pubmed-meshheading:2570073-Hydroxymethylglutaryl CoA Reductases, pubmed-meshheading:2570073-Hydroxymethylglutaryl-CoA Synthase, pubmed-meshheading:2570073-Mutation, pubmed-meshheading:2570073-Oleic Acid, pubmed-meshheading:2570073-Oleic Acids, pubmed-meshheading:2570073-Ovary, pubmed-meshheading:2570073-Plasmids, pubmed-meshheading:2570073-Promoter Regions, Genetic, pubmed-meshheading:2570073-Receptors, LDL, pubmed-meshheading:2570073-Transcription, Genetic, pubmed-meshheading:2570073-Transfection
pubmed:year
1989
pubmed:articleTitle
Loss of transcriptional repression of three sterol-regulated genes in mutant hamster cells.
pubmed:affiliation
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't