Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
41
pubmed:dateCreated
1996-11-19
pubmed:abstractText
We have previously demonstrated that the retinol-binding protein (RBP) gene is induced by retinoids in hepatoma cells. In this report, we define in greater detail the region that mediates the retinoic acid response of the gene. It consists of two degenerate retinoic acid response elements, separated by 30 nucleotides that encompass a GC-rich Sp1 consensus-like sequence. We demonstrate that the entire region, as well as each element taken singly, can bind the retinoic acid receptors as homo- and heterodimers with low affinity. However, only the entire region is able to confer retinoic acid inducibility to a heterologous promoter. We also show that the correct phasing of the DNA segment is necessary to achieve full responsiveness. Site-directed mutants in each element retained partial induction after transfection, while the double mutant was no longer responsive, suggesting that the two elements act synergistically. Mutational analysis of the Sp1 binding site and cotransfection experiments revealed that Sp1 or a related protein plays an important role in the transcription of the gene. Thus, the retinoic acid induction of the RBP gene is mediated by a novel and complex responsive unit formed by two distinct elements located in a specific sequence context and the interplay of the retinoid receptors with Sp1 is required for induction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25524-32
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8810324-Animals, pubmed-meshheading:8810324-Base Sequence, pubmed-meshheading:8810324-Binding Sites, pubmed-meshheading:8810324-COS Cells, pubmed-meshheading:8810324-Cell Line, pubmed-meshheading:8810324-Cercopithecus aethiops, pubmed-meshheading:8810324-DNA Footprinting, pubmed-meshheading:8810324-DNA Primers, pubmed-meshheading:8810324-DNA-Binding Proteins, pubmed-meshheading:8810324-Deoxyribonuclease I, pubmed-meshheading:8810324-Drosophila melanogaster, pubmed-meshheading:8810324-HeLa Cells, pubmed-meshheading:8810324-Humans, pubmed-meshheading:8810324-L Cells (Cell Line), pubmed-meshheading:8810324-Mice, pubmed-meshheading:8810324-Molecular Sequence Data, pubmed-meshheading:8810324-Mutagenesis, Site-Directed, pubmed-meshheading:8810324-Polymerase Chain Reaction, pubmed-meshheading:8810324-Promoter Regions, Genetic, pubmed-meshheading:8810324-Receptors, Retinoic Acid, pubmed-meshheading:8810324-Recombinant Fusion Proteins, pubmed-meshheading:8810324-Retinoid X Receptors, pubmed-meshheading:8810324-Retinol-Binding Proteins, pubmed-meshheading:8810324-Transcription Factors, pubmed-meshheading:8810324-Transfection, pubmed-meshheading:8810324-Tretinoin, pubmed-meshheading:8810324-Tumor Cells, Cultured
pubmed:year
1996
pubmed:articleTitle
Identification of a novel retinoic acid response element in the promoter region of the retinol-binding protein gene.
pubmed:affiliation
Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini, 5 80131 Napoli, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't