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| Status |
Public on Apr 30, 2023 |
| Title |
The KEAP1-NRF2 pathway regulates TFEB/TFE3-dependent lysosomal biogenesis [RNA-seq: 7dpf_larvae] |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Under homeostatic conditions, NRF2 is repressed by Kelch-like ECH-associated protein 1 (KEAP1). Here, we demonstrate that Keap1 deficiency induces Nrf2 activation and post-developmental lethality in zebrafish larvae. Loss of viability is preceded by severe liver abnormalities characterized by an accumulation of lysosomes. Mechanistically, we demonstrate that loss of Keap1 promotes aberrant activation of transcription factor EB (TFEB)/transcription factor binding to IGHM Enhancer 3 (TFE3)-dependent lysosomal biogenesis. Importantly, we find that NRF2-dependent regulation of lysosomal biogenesis is cell autonomous and evolutionarily conserved.
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| Overall design |
Zebrafish embryos were injected with CRISPR/Cas9 targetting genes at the single-cell stage. RNA was extracted and sequenced at 7dpf.
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| Contributor(s) |
Ong AJ, Brown K, Cox A |
| Citation(s) |
37216554 |
| |
| Submission date |
Apr 26, 2023 |
| Last update date |
Jul 30, 2023 |
| Contact name |
Andrew Cox |
| E-mail(s) |
andrew.cox@petermac.org
|
| Phone |
0402429160
|
| Organization name |
PeterMacCallum Cancer Centre
|
| Street address |
305 Grattan St
|
| City |
Melbourne |
| State/province |
Victoria |
| ZIP/Postal code |
3052 |
| Country |
Australia |
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| Platforms (1) |
| GPL20828 |
Illumina NextSeq 500 (Danio rerio) |
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| Samples (32)
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| This SubSeries is part of SuperSeries: |
| GSE230611 |
The KEAP1-NRF2 pathway regulates TFEB/TFE3-dependent lysosomal biogenesis |
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| Relations |
| BioProject |
PRJNA961973 |
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