Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Nucleic Acids Res
1997 Oct 15;2520:4132-8. doi: 10.1093/nar/25.20.4132.
Show Gene links
Show Anatomy links
Identification of essential nucleotides of the FP1 element responsible for enhancement of low density lipoprotein receptor gene transcription.
Dhawan P
,
Chang R
,
Mehta KD
.
???displayArticle.abstract???
Low density lipoprotein (LDL) receptor gene is regulated at the transcriptional level by the intracellular level of sterols in animal cells. We have recently identified a 20 bp long region (-145 to -126), designated Footprint 1 (FP1), participating in maximal expression of the human LDL receptor gene in the absence of sterols in HepG2 cells [Mehta, K. D., Chang, R., Underwood, J., Wise, J. and Kumar, A. (1996) J. Biol. Chem ., 271, 33616-33622]. To determine the minimal FP1 sequence and to define the critical nucleotides required for function, a series of single nucleotide substitutions were introduced in the FP1 region. Twenty-three independent mutations were analyzed by transfection into HepG2 cells. These studies localize the regulatory region to 14 bp and demonstrate the requirement for essential guanine nucleotides at positions -135 and -136 for FP1 function. Furthermore, transfection studies suggest that the FP1-dependent increase in reporter gene expression is possibly mediated through interaction with the sterol-regulatory element. UV cross-linking and Southwestern blot analysis identified FP1-binding factors of approximately 50 and 125 kDa, which we have denoted p50 and p125. Mutations of the critical guanine residues (-135/-136) decreased the formation of the specific protein-DNA complex with the FP1 sequence and abolished its binding to the p125. We conclude that direct interaction of the p125 factor with these nucleotides of the FP1 element potentially contributes to FP1-dependent induction of LDL receptor gene expression.
Auwerx,
Regulation of the low density lipoprotein receptor and hydroxymethylglutaryl coenzyme A reductase genes by protein kinase C and a putative negative regulatory protein.
1989, Pubmed
Auwerx,
Regulation of the low density lipoprotein receptor and hydroxymethylglutaryl coenzyme A reductase genes by protein kinase C and a putative negative regulatory protein.
1989,
Pubmed
Auwerx,
Involvement of second messengers in regulation of the low-density lipoprotein receptor gene.
1989,
Pubmed
Briggs,
Nuclear protein that binds sterol regulatory element of low density lipoprotein receptor promoter. I. Identification of the protein and delineation of its target nucleotide sequence.
1993,
Pubmed
Brown,
The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor.
1997,
Pubmed
Brown,
A receptor-mediated pathway for cholesterol homeostasis.
1986,
Pubmed
Chang,
In vivo role of the Sp1 site neighboring sterol-responsive element-1 in controlling low-density lipoprotein receptor gene expression.
1996,
Pubmed
,
Xenbase
Chodosh,
A single polypeptide possesses the binding and transcription activities of the adenovirus major late transcription factor.
1986,
Pubmed
Cuthbert,
Mitogenic stimulation alters the regulation of LDL receptor gene expression in human lymphocytes.
1990,
Pubmed
Goldstein,
Regulation of the mevalonate pathway.
1990,
Pubmed
Hamanaka,
Induction of low density lipoprotein receptor and a transcription factor SP-1 by tumor necrosis factor in human microvascular endothelial cells.
1992,
Pubmed
Hoffer,
The mouse low density lipoprotein receptor gene: cDNA sequence and exon-intron structure.
1993,
Pubmed
Hua,
SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element.
1993,
Pubmed
Kaytor,
Carbohydrate regulation of hepatic gene expression. Evidence against a role for the upstream stimulatory factor.
1997,
Pubmed
Liu,
Carbohydrate regulation of the rat L-type pyruvate kinase gene requires two nuclear factors: LF-A1 and a member of the c-myc family.
1993,
Pubmed
Lloyd,
Transcriptional modulators affect in vivo protein binding to the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase promoters.
1995,
Pubmed
Mazzone,
Relation of growth- and sterol-related regulatory pathways for low density lipoprotein receptor gene expression.
1990,
Pubmed
Mehta,
The low density lipoprotein receptor in Xenopus laevis. I. Five domains that resemble the human receptor.
1991,
Pubmed
,
Xenbase
Mehta,
Identification of a novel cis-acting element participating in maximal induction of the human low density lipoprotein receptor gene transcription in response to low cellular cholesterol levels.
1996,
Pubmed
Nicholson,
Transforming growth factor-beta up-regulates low density lipoprotein receptor-mediated cholesterol metabolism in vascular smooth muscle cells.
1992,
Pubmed
Sanchez,
Cooperation by sterol regulatory element-binding protein and Sp1 in sterol regulation of low density lipoprotein receptor gene.
1995,
Pubmed
Shih,
Definition of the carbohydrate response element of the rat S14 gene. Evidence for a common factor required for carbohydrate regulation of hepatic genes.
1992,
Pubmed
Singh,
Molecular cloning of an enhancer binding protein: isolation by screening of an expression library with a recognition site DNA.
1988,
Pubmed
Smith,
Identification of nucleotides responsible for enhancer activity of sterol regulatory element in low density lipoprotein receptor gene.
1990,
Pubmed
Stopeck,
Cytokine regulation of low density lipoprotein receptor gene transcription in HepG2 cells.
1993,
Pubmed
Streicher,
SREBP-1 mediates activation of the low density lipoprotein receptor promoter by insulin and insulin-like growth factor-I.
1996,
Pubmed
Südhof,
Three direct repeats and a TATA-like sequence are required for regulated expression of the human low density lipoprotein receptor gene.
1987,
Pubmed
Südhof,
42 bp element from LDL receptor gene confers end-product repression by sterols when inserted into viral TK promoter.
1987,
Pubmed
Wang,
Nuclear protein that binds sterol regulatory element of low density lipoprotein receptor promoter. II. Purification and characterization.
1993,
Pubmed
Wang,
SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis.
1994,
Pubmed
Yokoyama,
SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene.
1993,
Pubmed
