Promoter function and the role of cytokines in the transcriptional regulation of rabbit CYP2E1 and CYP2E2.
Arch Biochem Biophys
; 382(1): 129-37, 2000 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-11051106
Rabbit CYP2E1 and CYP2E2 show considerable similarity in the 5' flanking region, but a 32-base-pair element (32-BPE) that is repeated in 2E1 is present only as a single inexact copy in 2E2. In the present investigation, footprinting disclosed two specific binding sites for liver nuclear proteins, and the DNase I sensitivity profiles of the two genes were found to be different. Several positive and negative regulatory elements were identified by transfection with a series of constructs of upstream CYP2E sequences fused to the luciferase gene. Both genes have an HNF-1 consensus motif with one nucleotide mismatch, which affects binding affinity and promoter activity. Investigation of DNA-protein interactions revealed that Sp1 and NFkappaB bind exclusively to the 32-BPE of 2E1 and 2E2, respectively, suggesting a possible regulatory role for the 32-BPE. Interleukin-1alpha (IL-1alpha) gave rise to a 2.5-fold increase in the promoter activity of 2E1 in HepG2 cells, and the IL-1alpha-mediated induction of reporter gene expression was almost completely prevented when the 32-BPE was deleted. Increased DNA binding and Sp1 protein content as a result of IL-1alpha treatment, as well as cotransfection experiments with pPacSp1, suggest that Sp1 is a transcription activator for the induction of 2E1 by IL-1alpha in HepG2 cells.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Regulação Enzimológica da Expressão Gênica
/
Citocinas
/
Regiões Promotoras Genéticas
/
Citocromo P-450 CYP2E1
/
Sistema Enzimático do Citocromo P-450
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Arch Biochem Biophys
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos