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

Toxicology and Applied Pharmacology
Azhwar RaghunathEkambaram Perumal

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. ...Continue Reading

Citations

Mar 13, 2019·Basic & Clinical Pharmacology & Toxicology·Azhwar RaghunathEkambaram Perumal
Sep 5, 2019·Molecular Biology Reports·Lakshmikanthan PanneerselvamEkambaram Perumal
Sep 11, 2019·International Journal of Molecular Sciences·Tayaba IsmailHyun-Shik Lee
Feb 14, 2021·Animals : an Open Access Journal From MDPI·Christina MitsiopoulouEleni Tsiplakou

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