| First Author | Hirotsu Y | Year | 2012 |
| Journal | Nucleic Acids Res | Volume | 40 |
| Issue | 20 | Pages | 10228-39 |
| PubMed ID | 22965115 | Mgi Jnum | J:200275 |
| Mgi Id | MGI:5507955 | Doi | 10.1093/nar/gks827 |
| Citation | Hirotsu Y, et al. (2012) Nrf2-MafG heterodimers contribute globally to antioxidant and metabolic networks. Nucleic Acids Res 40(20):10228-39 |
| abstractText | NF-E2-related factor 2 (Nrf2) is a key transcription factor that is critical for cellular defense against oxidative and xenobiotic insults. Nrf2 heterodimerizes with small Maf (sMaf) proteins and binds to antioxidant response elements (AREs) to activate a battery of cytoprotective genes. However, it remains unclear to what extent the Nrf2-sMaf heterodimers contribute to ARE-dependent gene regulation on a genome-wide scale. We performed chromatin immunoprecipitation coupled with high-throughput sequencing and identified the binding sites of Nrf2 and MafG throughout the genome. Compared to sites occupied by Nrf2 alone, many sites co-occupied by Nrf2 and MafG exhibit high enrichment and are located in species-conserved genomic regions. The ARE motifs were significantly enriched among the recovered Nrf2-MafG-binding sites but not among the Nrf2-binding sites that did not display MafG binding. The majority of the Nrf2-regulated cytoprotective genes were found in the vicinity of Nrf2-MafG-binding sites. Additionally, sequences that regulate glucose metabolism and several amino acid transporters were identified as Nrf2-MafG target genes, suggesting diverse roles for the Nrf2-MafG heterodimer in stress response. These data clearly support the notion that Nrf2-sMaf heterodimers are complexes that regulate batteries of genes involved in various aspects of cytoprotective and metabolic functions through associated AREs. |
