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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
51
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pubmed:dateCreated |
2002-12-16
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pubmed:abstractText |
The Rev-erb and retinoic acid-related orphan receptors (ROR) are two related families of orphan nuclear receptors that recognize similar response elements but have opposite effects on transcription. Recently, the Rev-erbalpha gene promoter has been characterized and shown to harbor a functional Rev-erbalpha-binding site known as Rev-DR2, responsible for negative feedback down-regulation of promoter activity by Rev-erbalpha itself. The present study aimed to investigate whether Rev-erbalpha gene expression is regulated by RORalpha. Gel shift analysis demonstrated that in vitro translated hRORalpha1 protein binds to the Rev-DR2 site, both as monomer and dimer. Chromatin immunoprecipitation assays demonstrated that binding of RORalpha to this site also occurred in vivo in human hepatoma HepG2 cells. The Rev-DR2 site was further shown to be functional as it conferred hRORalpha1 responsiveness to a heterologous promoter and to the natural human Rev-erbalpha gene promoter in these cells. Mutation of this site in the context of the natural Rev-erbalpha gene promoter abolished its activation by RORalpha, indicating that this site plays a key role in hRORalpha1 action. Finally, adenoviral overexpression of hRORalpha1 in HepG2 cells led to enhanced hRev-erbalpha mRNA accumulation, further confirming the physiological importance of RORalpha1 in the regulation of Rev-erbalpha expression.
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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/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NR1D1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 1...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 1...,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RORA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
49275-81
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12377782-Adenoviridae,
pubmed-meshheading:12377782-Binding Sites,
pubmed-meshheading:12377782-Cell Line,
pubmed-meshheading:12377782-Chromatin,
pubmed-meshheading:12377782-DNA-Binding Proteins,
pubmed-meshheading:12377782-Dimerization,
pubmed-meshheading:12377782-Gene Expression Regulation,
pubmed-meshheading:12377782-Humans,
pubmed-meshheading:12377782-Mutation,
pubmed-meshheading:12377782-Nuclear Receptor Subfamily 1, Group D, Member 1,
pubmed-meshheading:12377782-Nuclear Receptor Subfamily 1, Group F, Member 1,
pubmed-meshheading:12377782-Plasmids,
pubmed-meshheading:12377782-Precipitin Tests,
pubmed-meshheading:12377782-Promoter Regions, Genetic,
pubmed-meshheading:12377782-Protein Binding,
pubmed-meshheading:12377782-Protein Biosynthesis,
pubmed-meshheading:12377782-RNA, Messenger,
pubmed-meshheading:12377782-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:12377782-Recombinant Proteins,
pubmed-meshheading:12377782-Time Factors,
pubmed-meshheading:12377782-Trans-Activators,
pubmed-meshheading:12377782-Transcription, Genetic,
pubmed-meshheading:12377782-Tretinoin
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pubmed:year |
2002
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pubmed:articleTitle |
Transcriptional regulation of human Rev-erbalpha gene expression by the orphan nuclear receptor retinoic acid-related orphan receptor alpha.
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pubmed:affiliation |
UR 545 INSERM, Institut Pasteur de Lille, 1 Rue du Pr. Calmette, 59019 Lille, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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