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Titolo:
New functional promoter polymorphism, CETP/-629, in cholesteryl eater transfer protein (CETP) gene related to CETP mass and high density lipoprotein cholesterol levels - Role of Sp1/Sp3 in transcriptional regulation
Autore:
Dachet, C; Poirier, O; Cambien, F; Chapman, J; Rouis, M;
Indirizzi:
Hop La Pitie Salpetriere, INSERM, U321, F-75651 Paris 13, France Hop La Pitie Salpetriere Paris France 13 U321, F-75651 Paris 13, France INSERM, U525, Paris, France INSERM Paris FranceINSERM, U525, Paris, France
Titolo Testata:
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
fascicolo: 2, volume: 20, anno: 2000,
pagine: 507 - 515
SICI:
1079-5642(200002)20:2<507:NFPPCI>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
ESTER TRANSFER PROTEIN; CORONARY HEART-DISEASE; PLASMA HDL-CHOLESTEROL; FACTORS SP1; BINDING PROTEIN; MUTATION; DEFICIENCY; EXPRESSION; MEN; ACTIVATION;
Keywords:
cholesteryl ester transfer protein; gene polymorphisms; transcription factors; ECTIM; cardiovascular disease;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Dachet, C Hop La Pitie Salpetriere, INSERM, U321, 83 Bd Hop, F-75651 Paris13, France Hop La Pitie Salpetriere 83 Bd Hop Paris France 13 s 13, France
Citazione:
C. Dachet et al., "New functional promoter polymorphism, CETP/-629, in cholesteryl eater transfer protein (CETP) gene related to CETP mass and high density lipoprotein cholesterol levels - Role of Sp1/Sp3 in transcriptional regulation", ART THROM V, 20(2), 2000, pp. 507-515

Abstract

A new polymorphism located at position -629 (CETP/-629A/C) in the promoterof the cholesteryl eater transfer protein (CETP) gene is described, The -629A allele was associated with lower CETP mass (P<0.0001) and higher high density lipoprotein cholesterol (P<0.001) than the C allele in a sample of 536 control subjects from the ECTIM study. Transfection studies in HepG2 cells with a luciferase expression vector incorporating a 777-bp fragment of the CETP promoter and containing either A or C at position -629 showed significantly lower luciferase activity with the promoter fragment of the A allele (-25%, P<0.05). By gel-shift assay, DNA-protein interactions were evaluated in nuclear extracts of HepG2 cells with the use of 2 probes (A or C probe) composed of 20 bp of the promoter sequence surrounding the polymorphic site. Two specific complexes of distinct migration rate were identified with the A and the C probe. Competition with an excess of oligonucleotide containing the Sp1 consensus binding site showed that a protein(s) of the Sp transcription factor family was implicated in complex formation with the A probe but not with the C probe. incubation with specific antibodies indicatedthat Sp1 and Sp3 bound specifically to the A probe. We introduced mutations in the -629-Sp1 binding site to test its functionality and to define the characteristics of transcription factor binding. We showed, by gel-shift assay, that no nuclear proteins bound to the mutated sequence. Transient transfection of HepG2 cells revealed that the expression of the mutated fragment was significantly increased compared with that of the A promoter fragment(25%, P<0.05). The mutated fragment displayed the same activity as that ofthe C promoter. These results indicate that Sp1 and/or Sp3 repress CETP promoter activity, whereas nuclear factors binding the C allele are without effect on promoter expression.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 01:37:19