Linked Life Data

8945636

Source:http://linkedlifedata.com/resource/pubmed/id/8945636

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1997-1-30
pubmed:abstractText
Retinoic acid (RA) is known to have potent effects on development and differentiation. RA exerts its effects on transcription through two distinct classes of nuclear receptors, the retinoic acid receptor (RAR) and the retinoid X receptor (RXR), that bind to specific RA-responsive elements (RARE) in target genes. alpha-Fetoprotein (AFP), a hepatocyte differentiation, maturation, and carcinogenesis marker, is transcriptionally upregulated by RA in McA-RH8994 hepatoma cells. Using deletion mapping analysis, we have identified a RARE-like sequence that is located between -2406 and -2378 of the transcription initiation site of the rat AFP gene. Sequence analysis demonstrated that this cis-acting element consists of three direct repeats and one inverted repeat of a GGGTCA-like half-site. The putative RARE can specifically bind to both RXR homodimers and RAR/RXR heterodimers as determined by gel mobility shift assays. A DR1 direct repeat was more efficient than a DR5 direct repeat oligonucleotide in competition for binding of the putative RARE to RXR and RAR/RXR. A mutagenesis study indicated that to have a full-strength induction, all the repeats were required. To further analyze the function of this element in vivo, a reporter gene construct of the putative RARE combined with the thymidine kinase promoter was cotransfected with RAR and RXR expression plasmids in CV1 cells. CAT assays demonstrated that overexpression of RXRalpha conferred the best RA response, consistent with our previous observation that 9-cis-RA is more potent than all-trans-RA for inducing the expression of the AFP gene. In addition, the RXR selective ligand LG100153 alone can stimulate the expression of the AFP gene. Our data suggest that an RXR-mediated pathway exists for modulation of AFP gene expression through a specific element.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1044-5498
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
955-63
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8945636-Animals, pubmed-meshheading:8945636-Base Sequence, pubmed-meshheading:8945636-Cell Line, pubmed-meshheading:8945636-Cercopithecus aethiops, pubmed-meshheading:8945636-Chloramphenicol O-Acetyltransferase, pubmed-meshheading:8945636-DNA-Binding Proteins, pubmed-meshheading:8945636-Gene Expression Regulation, pubmed-meshheading:8945636-Liver Neoplasms, Experimental, pubmed-meshheading:8945636-Molecular Sequence Data, pubmed-meshheading:8945636-Mutagenesis, Site-Directed, pubmed-meshheading:8945636-Oligodeoxyribonucleotides, pubmed-meshheading:8945636-Rats, pubmed-meshheading:8945636-Receptors, Retinoic Acid, pubmed-meshheading:8945636-Recombinant Fusion Proteins, pubmed-meshheading:8945636-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:8945636-Repetitive Sequences, Nucleic Acid, pubmed-meshheading:8945636-Retinoid X Receptors, pubmed-meshheading:8945636-Sequence Deletion, pubmed-meshheading:8945636-Transcription Factors, pubmed-meshheading:8945636-Transfection, pubmed-meshheading:8945636-Tretinoin, pubmed-meshheading:8945636-alpha-Fetoproteins
pubmed:year
1996
pubmed:articleTitle
RXR-mediated regulation of the alpha-fetoprotein gene through an upstream element.
pubmed:affiliation
Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.