title: All-trans retinoic acid inhibits the recruitment of ARNT to DNA, resulting in the decrease of CYP1A1 mRNA expression in HepG2 cells.
abstract: Aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) are well-conserved transcription factors among species. However, there are a very limited number of reports on the physiological function of AHR, particularly on the regulation of AHR by endogenous compounds. We hence investigated the effects of all-trans retinoic acid (atRA) on cytochrome P450 (CYP) 1A1 gene transcription as a model of AHR-regulated transcription mechanisms in HepG2 cells, a human hepatoma cell line. Treatment with atRA significantly reduced transactivation and expression of CYP1A1 mRNA to less than half of its control value, and this inhibitory effect was mediated by RARα. The result of chromatin immunoprecipitation assay indicated that treatment with atRA at 1-100 nM drastically inhibited the recruitment of ARNT to DNA regions containing xenobiotic responsive elements. In conclusion, atRA at physiological concentrations could reduce AHR-mediated gene transcription via the inhibition of recruitment of ARNT to relevant DNA regions.
authors.affiliation: Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, Sapporo, Japan.
authors.forename: Marumi
authors.initials: M
authors.lastname: Ohno
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ikenaka
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishizuka
mesh_terms: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006801:Humans; D047468:Immunoprecipitation; D012333:RNA, Messenger / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D015533:Transcriptional Activation / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology* / Q000502:physiology
chemical_list: C497396:ARNT protein, human; C000607071:RARA protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D014212:Tretinoin; D004247:DNA; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1