The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha
Open accessAbstract
Cellular oxidative and electrophilic stress triggers a protective response in mammals regulated by NRF2 (nuclear factor (erythroid-derived) 2-like; NFE2L2) binding to deoxyribonucleic acid-regulatory sequences near stress-responsive genes. Studies using Nrf2-deficient mice suggest that hundreds of genes may be regulated by NRF2. To identify human NRF2-regulated genes, we conducted chromatin immunoprecipitation (ChIP)-sequencing experiments in lymphoid cells treated with the dietary isothiocyanate, sulforaphane (SFN) and carried out follow-up biological experiments on candidates. We found 242 high confidence, NRF2-bound genomic regions and 96% of these regions contained NRF2-regulatory sequence motifs. The majority of binding sites were near potential novel members of the NRF2 pathway. Validation of selected candidate genes using parallel ChIP techniques and in NRF2-silenced cell lines indicated that the expression of about two-thirds of the candidates are likely to be directly NRF2-dependent including retinoid X receptor alpha (RXRA). NRF2 regulation of RXRA has implications for response to retinoid treatments and adipogenesis. In mouse, 3T3-L1 cells' SFN treatment affected Rxra expression early in adipogenesis, and knockdown of Nrf2-delayed Rxra expression, both leading to impaired adipogenesis.
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“Although NRF2 is the master regulator of oxidative stress response, including during human erythroblast differentiation (46), it is increasingly evident that NRF2 mediates the expression of genes involved in other diverse processes (21,68,84).”
Background
Cited by
Modulation of oxidative stress as an anticancer strategy
Gorrini, C., Harris, I. S., & Mak, T. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4002 · Cited by 3,579
Loboda, A., Damulewicz, M., Pyza, E., Jozkowicz, A., & Dulak, J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2223-0 · Cited by 2,632
NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis
Dodson, M., Castro-Portuguez, R., & Zhang, D. D. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101107 · Cited by 2,435
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
NRF2, 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
Metadata
- Authors
- Chorley, B. N., Campbell, M. R., Wang, X., Karaca, M., Sambandan, D., Bangura, F., Xue, P., Pi, J., Kleeberger, S. R., & Bell, D. A.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-05-11
- Volume
- 40
- Issue
- 15
- Pages
- 7416-7429
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W2140452134
- Cited by
- 558
- References
- 15
- FWCI
- 12.55
- Type
- journal article
- Language
- en
- Open access
- gold
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- Chorley, B. N., Campbell, M. R., Wang, X., Karaca, M., Sambandan, D., Bangura, F., Xue, P., Pi, J., Kleeberger, S. R., & Bell, D. A. (2012). Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha. Nucleic Acids Research. https://doi.org/10.1093/nar/gks409
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