PUBLICATION

Genome-wide identification and analysis of Nrf2 binding sites - Antioxidant response elements in zebrafish

Authors
Raghunath, A., Nagarajan, R., Sundarraj, K., Panneerselvam, L., Perumal, E.
ID
ZDB-PUB-180924-2
Date
2018
Source
Toxicology and applied pharmacology   360: 236-248 (Journal)
Registered Authors
Azhwar, Raghunath
Keywords
Antioxidant Response Element, Genome, Keap1/Nrf2/ARE Pathway, Nrf2 Binding Site, Oxidative Stress, Zebrafish
MeSH Terms
  • Animals
  • Antioxidant Response Elements/genetics*
  • Antioxidants/metabolism*
  • Binding Sites/drug effects
  • Binding Sites/genetics
  • Genome/genetics
  • Genome-Wide Association Study/methods
  • Genomics/methods
  • Isothiocyanates/pharmacology
  • Kelch-Like ECH-Associated Protein 1/genetics
  • NF-E2-Related Factor 2/genetics*
  • Oxidative Stress/drug effects
  • Oxidative Stress/genetics
  • Signal Transduction/drug effects
  • Signal Transduction/genetics
  • Transcription, Genetic/drug effects
  • Transcription, Genetic/genetics
  • Zebrafish
PubMed
30243843 Full text @ Tox. App. Pharmacol.
Abstract
In the post-genomic era, deciphering the Nrf2 binding sites - antioxidant response elements (AREs) is an essential task that underlies and governs the Keap1-Nrf2-ARE pathway - a cell survival response pathway to environmental stresses in the vertebrate model system. AREs regulate the transcription of a repertoire of phase II detoxifying and/or oxidative-stress responsive genes, offering protection against toxic chemicals, carcinogens, and xenobiotics. In order to identify and analyze AREs in zebrafish, a pattern search algorithm was developed to identify AREs and computational tools available online were utilized to analyze the identified AREs in zebrafish. This study identified the AREs within 30 kb upstream from the transcription start site of antioxidant genes and mitochondrial genes. We report for the first time the AREs of all the known protein coding genes in the zebrafish genome. Western blotting, RT2 profiler array PCR, and qRT-PCR were performed to test whether AREs influence the Nrf2 target genes expression in the zebrafish larvae using sulforaphane. This study reveals unique AREs that have not been previously reported in the cytoprotective genes. Nine TGAG/CNNNTC and six TGAG/CNNNGC AREs were observed significantly. Our findings suggest that AREs drive the dynamic transcriptional events of Nrf2 target genes in the zebrafish larvae on exposure to sulforaphane. The identified abundant putative AREs will define the Keap1-Nrf2-ARE network and elucidate the precise regulation of Nrf2-ARE pathway in not only diseases but also in embryonic development, inflammation, and aerobic respiration. Our results help to understand the dynamic complexity of the Nrf2-ARE system in zebrafish.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping