New insights into the regulation of cytochrome P450 2C9 gene expression: the role of the transcription factor GATA-4

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F10%3A10080502" target="_blank" >RIV/00179906:_____/10:10080502 - isvavai.cz</a>

Výsledek na webu

—

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

New insights into the regulation of cytochrome P450 2C9 gene expression: the role of the transcription factor GATA-4

Popis výsledku v původním jazyce

CYP2C9 is an important drug-metabolizing enzyme. However, its endogenous regulation is largely unknown. We examined the role of GATA transcription factors in the gene expression of CYP2C9. We investigated four putative GATA binding sites within the first200bp of CYP2C9 promoter at the positions I: -173/-170, II: -167/-164, III: -118/-115, and IV: -106/-103. Luciferase activity driven by a wild-type CYP2C9 promoter construct was strongly up-regulated in Huh-7 cells co-transfected with GATA-2 and GATA-4,whereas mutations introduced into GATA binding site III or I and II reduced this induction significantly. Electrophoretic mobility shift assays revealed specific binding of GATA-4 and GATA-6 to the oligonucleotides containing GATA binding sites I and II. Furthermore, the association of GATA-4 with CYP2C9 promoter was confirmed by chromatin immunoprecipitation in HepG2 cells. These data strongly suggest an involvement of GATA-4 in the transcriptional regulation of CYP2C9. 10.1124/dmd.109

Název v anglickém jazyce

New insights into the regulation of cytochrome P450 2C9 gene expression: the role of the transcription factor GATA-4

Popis výsledku anglicky

CYP2C9 is an important drug-metabolizing enzyme. However, its endogenous regulation is largely unknown. We examined the role of GATA transcription factors in the gene expression of CYP2C9. We investigated four putative GATA binding sites within the first200bp of CYP2C9 promoter at the positions I: -173/-170, II: -167/-164, III: -118/-115, and IV: -106/-103. Luciferase activity driven by a wild-type CYP2C9 promoter construct was strongly up-regulated in Huh-7 cells co-transfected with GATA-2 and GATA-4,whereas mutations introduced into GATA binding site III or I and II reduced this induction significantly. Electrophoretic mobility shift assays revealed specific binding of GATA-4 and GATA-6 to the oligonucleotides containing GATA binding sites I and II. Furthermore, the association of GATA-4 with CYP2C9 promoter was confirmed by chromatin immunoprecipitation in HepG2 cells. These data strongly suggest an involvement of GATA-4 in the transcriptional regulation of CYP2C9. 10.1124/dmd.109

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

—

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2010

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Drug Metabolism and Disposition

ISSN

0090-9556

e-ISSN

—

Svazek periodika

38

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

—

Kód UT WoS článku

000274591400008

EID výsledku v databázi Scopus

—