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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
33
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pubmed:dateCreated |
2004-8-9
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pubmed:abstractText |
Activation of phosphoenolpyruvate carboxykinase (PEPCK) gene transcription in response to all-trans-retinoic acid (RA) or a glucocorticoid such as dexamethasone (Dex) requires a distinct arrangement of DNA-response elements and their cognate transcription activators on the gene promoter. Two of the accessory factor-binding elements involved in the Dex response (gAF1 and gAF3) coincide with the DNA-response elements involved in the RA response. We demonstrate here that the combination of Dex/RA has a synergistic effect on endogenous PEPCK gene expression in rat hepatocytes and H4IIE hepatoma cells. Reporter gene studies show that the gAF3 element and one of the two glucocorticoid receptor-binding elements (GR1) are most important for this effect. Chromatin immunoprecipitation assays revealed that when H4IIE cells were treated with Dex/RA, ligand-activated retinoic acid receptors (retinoic acid receptor/retinoid X receptor) and glucocorticoid receptors are recruited to this gene promoter, as are the transcription coregulators p300, CREB-binding protein, p/CIP, and SRC-1. Notably, the recruitment of p300 and RNA polymerase II to the PEPCK promoter is increased by the combined Dex/RA treatment compared with Dex or RA treatment alone. The functional importance of p300 in the Dex/RA response is illustrated by the observation that selective reduction of this coactivator, but not that of CREB-binding protein, abolishes the synergistic effect in H4IIE cells.
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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/Antineoplastic Agents, Hormonal,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/E1A-Associated p300 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Ep300 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoenolpyruvate Carboxykinase...,
http://linkedlifedata.com/resource/pubmed/chemical/RNA Polymerase II,
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 |
Aug
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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 |
13
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
34191-200
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15166231-Animals,
pubmed-meshheading:15166231-Antineoplastic Agents, Hormonal,
pubmed-meshheading:15166231-Blotting, Western,
pubmed-meshheading:15166231-Carcinoma, Hepatocellular,
pubmed-meshheading:15166231-Cell Line,
pubmed-meshheading:15166231-Cell Line, Tumor,
pubmed-meshheading:15166231-Chromatin,
pubmed-meshheading:15166231-Dexamethasone,
pubmed-meshheading:15166231-Drug Synergism,
pubmed-meshheading:15166231-E1A-Associated p300 Protein,
pubmed-meshheading:15166231-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:15166231-Genes, Reporter,
pubmed-meshheading:15166231-Glucocorticoids,
pubmed-meshheading:15166231-Hepatocytes,
pubmed-meshheading:15166231-Humans,
pubmed-meshheading:15166231-Ligands,
pubmed-meshheading:15166231-Liver,
pubmed-meshheading:15166231-Liver Neoplasms,
pubmed-meshheading:15166231-Luciferases,
pubmed-meshheading:15166231-Mutation,
pubmed-meshheading:15166231-Nuclear Proteins,
pubmed-meshheading:15166231-Phosphoenolpyruvate Carboxykinase (ATP),
pubmed-meshheading:15166231-Plasmids,
pubmed-meshheading:15166231-Precipitin Tests,
pubmed-meshheading:15166231-Promoter Regions, Genetic,
pubmed-meshheading:15166231-Protein Structure, Tertiary,
pubmed-meshheading:15166231-RNA Polymerase II,
pubmed-meshheading:15166231-Rats,
pubmed-meshheading:15166231-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15166231-Trans-Activators,
pubmed-meshheading:15166231-Transfection,
pubmed-meshheading:15166231-Tretinoin
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pubmed:year |
2004
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pubmed:articleTitle |
The synergistic effect of dexamethasone and all-trans-retinoic acid on hepatic phosphoenolpyruvate carboxykinase gene expression involves the coactivator p300.
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pubmed:affiliation |
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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