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

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About: New insights into the regulation of cytochrome P450 2C9 gene expression: the role of the transcription factor GATA-4 Goto Sponge NotDistinct Permalink

An Entity of Type : http://linked.opendata.cz/ontology/domain/vavai/Vysledek, within Data Space : linked.opendata.cz associated with source document(s)

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	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 first 200bp 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.109.029405 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 first 200bp 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.109.029405 (en)
Title	New insights into the regulation of cytochrome P450 2C9 gene expression: the role of the transcription factor GATA-4 New insights into the regulation of cytochrome P450 2C9 gene expression: the role of the transcription factor GATA-4 (en)
skos:prefLabel	New insights into the regulation of cytochrome P450 2C9 gene expression: the role of the transcription factor GATA-4 New insights into the regulation of cytochrome P450 2C9 gene expression: the role of the transcription factor GATA-4 (en)
skos:notation	RIV/00179906:_____/10:10080502!RIV11-MZ0-00179906
http://linked.open...avai/riv/aktivita	N
http://linked.open...avai/riv/aktivity	N
http://linked.open...iv/cisloPeriodika	3
http://linked.open...vai/riv/dodaniDat	2011
http://linked.open...aciTvurceVysledku	Nekvindová, Jana
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Fakultní nemocnice Hradec Králové
http://linked.open...dnocenehoVysledku	274697
http://linked.open...ai/riv/idVysledku	RIV/00179906:_____/10:10080502
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	gene expression; transcription factor; GATA; CYP2C9; cytochrome P450 (en)
http://linked.open.../riv/klicoveSlovo	gene expression CYP2C9 cytochrome P450 transcription factor GATA
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[165028AAAD03]
http://linked.open...i/riv/nazevZdroje	Drug Metabolism and Disposition
http://linked.open...in/vavai/riv/obor	EB
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	8 (xsd:int)
http://linked.open...UplatneniVysledku	2010
http://linked.open...v/svazekPeriodika	38
http://linked.open...iv/tvurceVysledku	Nekvindová, Jana Ingelman-Sundberg, Magnus Mkrtchian, Souren Cavaco, Isa Hofmann, Yvonne Landman, Ellie Mwinyi, Jessica Pedersen, Rasmus Steen
http://linked.open...ain/vavai/riv/wos	000274591400008
issn	0090-9556
number of pages	7 (xsd:int)

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