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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
1995-4-25
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pubmed:abstractText |
Liver-specific expression of the apolipoprotein AI (apoAI) gene is mediated by transcription factors bound to three sites (A, B, and C) in the apoAI enhancer. Sites A and C bind various members of the nuclear receptor superfamily, including the orphan nuclear receptor apolipoprotein regulatory protein-1 (ARP-1); site B binds the liver-enriched factor hepatic nuclear factor-3. The immediate early growth response factor (Egr-1), which is transiently expressed in various pathophysiologic states of the liver, activates the apoAI enhancer and overcomes ARP-1-mediated repression of the enhancer in hepatoblastoma HepG2 cells. Deletion mapping analysis revealed two Egr-1 binding sites, E1 and E2, flanking site A. Erg-1 bound efficiently to both E1 and E2. Sp1 in HepG2 nuclear extracts bound to E2 but not E1. In HepG2 cells, E1 functioned as an Egr-1 response element, whereas E2 had high basal activity and was not further induced by Egr-1. Mutations that prevent Egr-1 binding to the apoAI enhancer abolished its responsiveness to Erg-1, while they had only minor effects on its constitutive activity. These mutations also diminished the ability of Egr-1 to overcome ARP-1-mediated repression. Elimination of transcription factor binding to sites A, B, or C reduced enhancer activity without affecting Egr-1-dependent activation. We argue that Egr-1 is recruited to the apoAI enhancer complex under unusual circumstances, such as those prevailing during liver regeneration, to maintain apoAI transcription levels by overriding prior transcriptional controls.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoprotein A-I,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/EGR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Early Growth Response Protein 1,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
270
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7004-10
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:7896852-Apolipoprotein A-I,
pubmed-meshheading:7896852-Base Sequence,
pubmed-meshheading:7896852-DNA-Binding Proteins,
pubmed-meshheading:7896852-Early Growth Response Protein 1,
pubmed-meshheading:7896852-Enhancer Elements, Genetic,
pubmed-meshheading:7896852-Gene Expression Regulation,
pubmed-meshheading:7896852-Humans,
pubmed-meshheading:7896852-Immediate-Early Proteins,
pubmed-meshheading:7896852-Molecular Sequence Data,
pubmed-meshheading:7896852-Sp1 Transcription Factor,
pubmed-meshheading:7896852-Transcription, Genetic,
pubmed-meshheading:7896852-Transcription Factors
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pubmed:year |
1995
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pubmed:articleTitle |
Involvement of early growth response factor Egr-1 in apolipoprotein AI gene transcription.
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pubmed:affiliation |
Department of Cardiovascular Molecular Biology, Lederle Laboratories, Pearl River, New York 10965.
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pubmed:publicationType |
Journal Article
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