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| Status |
Public on Jun 18, 2012 |
| Title |
Identification of Novel NRF2-Regulated Genes by ChIPSeq |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Cellular oxidative and electrophilic stress triggers a protective response in mammals regulated by NRF2 (nuclear factor (erythroid-derived) 2-like; NFE2L2) binding to DNA-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 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 RXRAhas 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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| |
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| Overall design |
ChIP-Seq analysis of NRF2 binding sites in human lymphoblastoid cells treated with sulforaphane or vehicle
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| |
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| Contributor(s) |
Chorley BN, Campbell MR, Wang X, Bell DA |
| Citation(s) |
22581777, 30195190 |
| Submission date |
Apr 25, 2012 |
| Last update date |
Jan 08, 2020 |
| Contact name |
Xuting Wang |
| E-mail(s) |
wang21@niehs.nih.gov
|
| Phone |
9842873840
|
| Organization name |
NIEHS/NIH
|
| Street address |
111 TW Alexander Dr
|
| City |
Research Triangle Park |
| State/province |
NC |
| ZIP/Postal code |
27709 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
|
| Samples (12)
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| Relations |
| SRA |
SRP012507 |
| BioProject |
PRJNA161889 |
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