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rdf:type |
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lifeskim:mentions |
umls-concept:C0012854,
umls-concept:C0017337,
umls-concept:C0040845,
umls-concept:C0086222,
umls-concept:C0086418,
umls-concept:C0127400,
umls-concept:C0205112,
umls-concept:C0950109,
umls-concept:C1514562,
umls-concept:C1705733,
umls-concept:C1948020
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pubmed:issue |
1
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pubmed:dateCreated |
2007-10-15
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pubmed:abstractText |
Retinoic acid (RA) upregulates expression of PDGF ligands and receptors in neonatal rat lung fibroblasts, a process likely to promote maturation of the lung alveolus and possibly microstructures of other organs. A mutational analysis of the gene encoding the PDGF-A ligand has identified a complex retinoic acid response element (RARE) located far upstream of the transcription start site, in a 5'-distal enhanceosome region previously shown to harbor basal and vitamin D-inducible enhancer activity. Maximal RA responsiveness (fourfold) was conferred by nucleotide sequence located between -7064 and -6787, with a variety of deletion and point mutations revealing the importance of at least three nuclear receptor half-sites within the enhancer region (-6851 to -6824), as well as nucleotides located further upstream. Recombinant human retinoic acid receptor/retinoid-X receptor heterodimers bound with high affinity and sequence specificity to multiple regions within the RARE, as demonstrated by electrophoretic mobility shift and DNase I footprinting assays. The addition of RARE activity to previously described functions of the 5'-distal enhanceosome underscores the importance of this region as a key integration point for regulatory control of PDGF-A expression.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoid X Receptor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin D,
http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor A,
http://linkedlifedata.com/resource/pubmed/chemical/retinoic acid receptor alpha
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pubmed:status |
MEDLINE
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pubmed:issn |
1052-2166
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-12
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:17933214-5' Flanking Region,
pubmed-meshheading:17933214-Base Sequence,
pubmed-meshheading:17933214-Cell Line,
pubmed-meshheading:17933214-DNA,
pubmed-meshheading:17933214-Dose-Response Relationship, Drug,
pubmed-meshheading:17933214-Enhancer Elements, Genetic,
pubmed-meshheading:17933214-Genes, Reporter,
pubmed-meshheading:17933214-Humans,
pubmed-meshheading:17933214-Luciferases,
pubmed-meshheading:17933214-Molecular Sequence Data,
pubmed-meshheading:17933214-Platelet-Derived Growth Factor,
pubmed-meshheading:17933214-RNA, Messenger,
pubmed-meshheading:17933214-Receptors, Retinoic Acid,
pubmed-meshheading:17933214-Recombinant Proteins,
pubmed-meshheading:17933214-Response Elements,
pubmed-meshheading:17933214-Retinoid X Receptor alpha,
pubmed-meshheading:17933214-Transfection,
pubmed-meshheading:17933214-Tretinoin,
pubmed-meshheading:17933214-Vitamin D
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pubmed:year |
2007
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pubmed:articleTitle |
Retinoic acid inducibility of the human PDGF-a gene is mediated by 5'-distal DNA motifs that overlap with basal enhancer and vitamin D response elements.
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pubmed:affiliation |
Department of Molecular and Biomedical Pharmacology, University of Kentucky College of Medicine, Lexington, KY 40536-0298, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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