Premium
Selective cytochrome P450 1A1 but not 1B1 promoterCpG island DNA methylation by 6‐formylindolo[3,2‐b]carbazole (FICZ)
Author(s) -
Ghaedi Afsaneh,
Keshavarzi Majid,
Ghafarian Bahraman Ali,
MohammadiBardbori Afshin
Publication year - 2020
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22414
Subject(s) - aryl hydrocarbon receptor , cyp1b1 , chemistry , dna methylation , cytochrome p450 , regulation of gene expression , gene expression , epigenetics , methylation , gene , microbiology and biotechnology , dna methyltransferase , biochemistry , enzyme , biology , transcription factor
Epigenetic alterations are essential for normal mammalian development and regulation of gene expression. In this study, we aimed to determine if an enigmatic endogenous ligand of the aryl hydrocarbon receptor (AHR), 6‐formylindolo[3,2‐b]carbazole (FICZ), and methionine (Meth) have an epigenetic impact on AHR‐regulated cytochrome P450 1A1 and B1 ( CYP1A1 and CYP1B1 ) gene expression. Human hepatoma (HepG2‐XRE‐Luc and huh7) cells were exposed to FICZ in a medium with and without Meth supplementation. Selective and transient silencing of CYP1A1 but not CYP1B1 were seen by FICZ. Here we found that FICZ transiently represses CYP1A1 by targeting DNA (cytosine‐5)‐methyltransferase 3A ( DNMT3A ) and concomitant DNA methylation of the CYP1A1 promoter gene. Treatments with 5‐aza‐dC augmented CYP1A1 transcription activity. Our results reveal a new mechanism for transient activation of AHR by FICZ that can negatively and positively influence gene expression, and highlight the regulatory role of Meth on the CYP1A1 gene expression.