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Titolo:
TRANSCRIPTIONAL ACTIVATION OF THE CHOLESTEROL 7-ALPHA-HYDROXYLASE GENE (CYP7A) BY NUCLEAR HORMONE RECEPTORS
Autore:
CRESTANI M; SADEGHPOUR A; STROUP D; GALLI G; CHIANG JYL;
Indirizzi:
NE OHIO UNIV,COLL MED,DEPT BIOCHEM & MOL PATHOL,POB 95 ROOTSTOWN OH 44272 NE OHIO UNIV,COLL MED,DEPT BIOCHEM & MOL PATHOL ROOTSTOWN OH 44272 UNIV MILAN,INST PHARMACOL SCI,SCH PHARM I-20133 MILAN ITALY
Titolo Testata:
Journal of lipid research
fascicolo: 11, volume: 39, anno: 1998,
pagine: 2192 - 2200
SICI:
0022-2275(1998)39:11<2192:TAOTC7>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
RETINOIC ACID RECEPTORS; FACTOR COUP-TF; MESSENGER-RNA; PROMOTER; EXPRESSION; RAT; LIVER; ELEMENTS; METABOLISM; MUTATIONS;
Keywords:
BILE ACID RESPONSE ELEMENT; GENE TRANSCRIPTION AND REGULATION; NUCLEAR HORMONE RECEPTOR; BILE ACID SYNTHESIS; CYTOCHROME P450; CHOLESTEROL 7-ALPHA-HYDROXYLASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
45
Recensione:
Indirizzi per estratti:
Citazione:
M. Crestani et al., "TRANSCRIPTIONAL ACTIVATION OF THE CHOLESTEROL 7-ALPHA-HYDROXYLASE GENE (CYP7A) BY NUCLEAR HORMONE RECEPTORS", Journal of lipid research, 39(11), 1998, pp. 2192-2200

Abstract

The gene encoding cholesterol 7 alpha-hydroxylase (CYP7A), the rate-limiting enzyme in bile acid synthesis, is transcriptionally regulated by bile acids and hormones. Previously, we have identified two bile acid response elements (BARE) in the promoter of the CYP7A gene, The BARE II is located in nt -149/-118 region and contains three hormone response element (HRE)-like sequences that form two overlapping nuclear receptor binding sites. One is a direct repeat separated by one nucleotide DR1 (-146-TGGACTtAGTTCA-134) and the other is a direct repeat separated by five nucleotides DR5 (-139-AGTTCAaggccGGG TAA-123). Mutagenesis of these HRE sequences resulted in lower transcriptional activity ofthe CYP7A promoter/reporter genes in transient transfection assay in HepG2 cells. The orphan nuclear receptor, hepatocyte nuclear factor 4 (HNF-4)(1), binds to the DR1 sequence as assessed by electrophoretic mobility shift assay, and activates the CYP7A promoter/reporter activity by about 9-fold. Cotransfection of HNF-4 plasmid with another orphannuclear receptor, chicken ovalbumin upstream promoter-transcription factor LI (COUP-TRI), synergistically activated the CYP7A transcriptionby 80-fold. The DR5 binds the RXR/RAR heterodimer, A hepatocyte nuclear factor-3 (HNF-3) binding site (-175-TGTTTGTTCT-166) was identified. HNF-3 was required for both basal transcriptional activity and stimulation of the rat CYP7A promoter activity by retinoic acid, Combinatorial interactions and binding of these transcription factors to BAREs may modulate the promoter activity and also mediate bile acid repressionof CYP7A gene transcription.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 12:05:11