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| Status |
Public on Dec 07, 2020 |
| Title |
The transcriptional coactivator CBP/p300 is an evolutionarily conserved node that promotes longevity in response to mitochondrial stress [HepG2] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Organisms respond to mitochondrial stress by activating multiple defense pathways including the mitochondrial unfolded protein response (UPRmt). However, how different layers of UPRmt regulators are orchestrated to transcriptionally activate the stress responses remains largely unknown. Here we identified CBP-1, the worm ortholog of the mammalian acetyltransferases CBP/p300, as an essential regulator for UPRmt activation, as well as for mitochondrial stress-induced immune response, amyloid-β aggregation reduction and lifespan extension in Caenorhabditis elegans. Mechanistically, CBP-1 acts downstream of histone demethylases, JMJD-1.2/JMJD-3.1, and upstream of UPRmt transcription factors including ATFS-1, to systematically induce a broad spectrum of UPRmt genes and execute multiple beneficial functions. In mouse and human populations, transcript levels of CBP/p300 positively correlate with UPRmt transcripts and longevity. Furthermore, CBP/p300 inhibition disrupts, while forced expression of p300 is sufficient to activate, the UPRmt in mammalian cells. These results highlight an evolutionarily conserved mechanism that determines mitochondrial stress response, and promotes health and longevity through CBP/p300.
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| Overall design |
Human HepG2 cells treated with or without CBP/p300 Inhibitor A-485 and/or Dox
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| Contributor(s) |
Li TY, Bou Sleiman MS, Li H, Gao AW, Mottis A, Bachmann A, Schoonjans K, Auwerx J |
| Citation(s) |
33718883 |
| Submission date |
Aug 25, 2020 |
| Last update date |
Mar 23, 2021 |
| Contact name |
Terytty Yang Li |
| E-mail(s) |
terytty-yang.li@epfl.ch
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| Organization name |
EPFL
|
| Street address |
EPFL SV IBI-SV LISP AI 1145
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| City |
Lausanne |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
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| Platforms (1) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE131616 |
The transcriptional coactivator CBP/p300 is an evolutionarily conserved node that promotes longevity in response to mitochondrial stress |
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| Relations |
| BioProject |
PRJNA659242 |
| SRA |
SRP278825 |
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