Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1995-8-3
pubmed:abstractText
Feedback regulation of transcription from the low density lipoprotein (LDL) receptor gene is fundamentally important in the maintenance of intracellular sterol balance. The region of the LDL receptor promoter responsible for normal sterol regulation contains adjacent binding sites for the ubiquitous transcription factor Sp1 and the cholesterol-sensitive sterol regulatory element-binding proteins (SREBPs). Interestingly, both are essential for normal sterolmediated regulation of the promoter. The cooperation by Sp1 and SREBP-1 occurs at two steps in the activation process. SREBP-1 stimulates the binding of Sp1 to its adjacent recognition site in the promoter followed by enhanced stimulation of transcription after both proteins are bound to DNA. In the present report, we have defined the protein domains of Sp1 that are required for both synergistic DNA binding and transcriptional activation. The major activation domains of Sp1 that have previously been shown to be essential to activation of promoters containing multiple Sp1 sites are required for activation of the LDL receptor promoter. Additionally, the C domain is also crucial. This slightly acidic approximately 120-amino acid region is not required for efficient synergistic activation by multiple Sp1 sites or in combination with other recently characterized transcriptional regulators. We also show that Sp1 domain C is essential for full, enhanced DNA binding by SREBP-1. Taken together with other recent studies on the role of Sp1 in promoter activation, the current experiments suggest a unique combinatorial mechanism for promoter activation by two distinct transcription factors that are both essential to intracellular cholesterol homeostasis.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-1885006, http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-2298751, http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-2512012, http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-3030558, http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-3142690, http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-3277969, http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-3513311, http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-3611089, http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-7836375, http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-7935378, http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-8006035, http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-8253080, http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-8330738, http://linkedlifedata.com/resource/pubmed/commentcorrection/7597088-8390995
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6102-6
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:7597088-Animals, pubmed-meshheading:7597088-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:7597088-Cell Line, pubmed-meshheading:7597088-Cloning, Molecular, pubmed-meshheading:7597088-DNA-Binding Proteins, pubmed-meshheading:7597088-Drosophila melanogaster, pubmed-meshheading:7597088-Escherichia coli, pubmed-meshheading:7597088-Feedback, pubmed-meshheading:7597088-Gene Expression Regulation, pubmed-meshheading:7597088-Helix-Loop-Helix Motifs, pubmed-meshheading:7597088-Kinetics, pubmed-meshheading:7597088-Leucine Zippers, pubmed-meshheading:7597088-Luciferases, pubmed-meshheading:7597088-Nuclear Proteins, pubmed-meshheading:7597088-Promoter Regions, Genetic, pubmed-meshheading:7597088-Receptors, LDL, pubmed-meshheading:7597088-Recombinant Proteins, pubmed-meshheading:7597088-Sp1 Transcription Factor, pubmed-meshheading:7597088-Sterol Regulatory Element Binding Protein 1, pubmed-meshheading:7597088-TATA Box, pubmed-meshheading:7597088-Transcription, Genetic, pubmed-meshheading:7597088-Transcription Factors, pubmed-meshheading:7597088-Transfection
pubmed:year
1995
pubmed:articleTitle
Domains of transcription factor Sp1 required for synergistic activation with sterol regulatory element binding protein 1 of low density lipoprotein receptor promoter.
pubmed:affiliation
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717-3900, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't