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The transcription factor GATA-4 regulates cytochrome P4502C19 gene expression

Publication |
2010

Abstract

Cytochrome P450 2C19 (CYP2C19) is an important enzyme involved in the metabolism of antiulcer drugs and antidepressants. However, despite the well documented drug-dependent variability of CYP2C19 expression, the mechanisms underlying the regulation of the enzyme remain unknown.

In this study we investigated whether the transcription factor family GATA is involved in the regulation of CYP2C19 gene expression. We identified a novel putative GATA binding site at position -165/-156 within the CYP2C19 gene promoter and performed luciferase gene reporter assays, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitations (ChIP) to document a sequence-specific interaction of GATA proteins with this putative GATA binding site.

The data obtained indicate that GATA-4 plays an important role in the transcriptional regulation of CYP2C19 expression. 10.1016/j.lfs.2010.02.021