Transcriptional regulation of rat gamma-glutamate cysteine ligase catalytic subunit gene is mediated through a distal antioxidant response element.

ABSTRACT: Despite it being a quintessential Phase II detoxification gene, the transcriptional regulation of the rat gamma-glutamate cysteine ligase catalytic subunit (GCLC) is controversial. Computer-based sequence analysis identified three putative antioxidant response elements (AREs) at positions -889 to -865 (ARE1), -3170 to -3146 (ARE2) and -3901 to -3877 (ARE3) in the 5'-flanking region of the transcriptional start site. Transfections of individual ARE-luciferase reporter gene constructs into H4IIE cells, a rat hepatoma cell line, identified ARE3 as the functional promoter. Chromatin immunoprecipitation assays using primary rat hepatocytes showed that the transcription factor Nrf2, which is known to regulate ARE-mediated genes, is associated with ARE3. Co-transfection of H4IIE cells with lucife

SUBMITTER: Shenvi SV 

PROVIDER: S-EPMC2756302 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature