Identification of pregnane-X receptor target genes and coactivator and corepressor binding to promoter elements in human hepatocytes.

ABSTRACT: Chromatin immunoprecipitation (ChIP) studies were conducted in human hepatocytes treated with rifampicin in order to identify new pregnane-X receptor (PXR) target genes. Genes, both previously known to be involved and not known to be involved in drug disposition, with PXR response elements (PXREs) located upstream, within or downstream from their potentially associated genes, were identified. Validation experiments identified several new drug disposition genes with PXR binding sites. Of these, only CYP4F12 demonstrated increased binding in the presence of rifampicin. The role of PXR in the basal and inductive response of CYP4F12 was confirmed in hepatocytes in which PXR was silenced. We also assessed the association of PXR-coactivators and -corepressors with known and newly identified PXRE

SUBMITTER: Hariparsad N 

PROVIDER: S-EPMC2651806 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature