The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Nrf2–MafG heterodimers contribute globally to antioxidant and metabolic networks
Open accessAbstract
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.
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Cites
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Self-citationCell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway
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Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming
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“The colors of the heat map reflect the log(2)-fold-change values relative to the mean expression level of each gene in the DMSO-treated (Veh) Hepa1 cells.”
BackgroundStructural basis for defects of Keap1 activity provoked by its point mutations in lung cancer
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BackgroundSelf-citationAnaplerotic roles of pyruvate carboxylase in mammalian tissues
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Cited by
The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis
Yamamoto, M., Kensler, T. W., & Motohashi, H. (2018) · Physiological Reviews · doi:10.1152/physrev.00023.2017 · Cited by 1,968
Self-citationNrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription
Kobayashi, E. H., Suzuki, T., Funayama, R., Nagashima, T., Hayashi, M., Sekine, H., Tanaka, N., Moriguchi, T., Motohashi, H., Nakayama, K., et al. (2016) · Nature Communications · doi:10.1038/ncomms11624 · Cited by 1,878
Self-citationNRF2, a Transcription Factor for Stress Response and Beyond
He, F., Ru, X., & Wen, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134777 · Cited by 1,820
The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway
Baird, L., & Yamamoto, M. (2020) · Molecular and Cellular Biology · doi:10.1128/mcb.00099-20 · Cited by 1,542
Self-citationDissecting molecular cross-talk between Nrf2 and NF-κB response pathways
Wardyn, J. D., Ponsford, A. H., & Sanderson, C. M. (2015) · Biochemical Society Transactions · doi:10.1042/bst20150014 · Cited by 1,200
Metadata
- Authors
- Hirotsu, Y., Katsuoka, F., Funayama, R., Nagashima, T., Nishida, Y., Nakayama, K., Douglas Engel, J., & Yamamoto, M.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-09-08
- Volume
- 40
- Issue
- 20
- Pages
- 10228-10239
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W2152175948
- Cited by
- 431
- References
- 10
- FWCI
- 6.39
- Type
- journal article
- Language
- en
- Open access
- gold
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- Hirotsu, Y., Katsuoka, F., Funayama, R., Nagashima, T., Nishida, Y., Nakayama, K., Douglas Engel, J., & Yamamoto, M. (2012). Nrf2–MafG heterodimers contribute globally to antioxidant and metabolic networks. Nucleic Acids Research. https://doi.org/10.1093/nar/gks827
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