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| Status |
Public on Oct 16, 2012 |
| Title |
SIRT3 functions in the nucleus in the control of stress-related gene expression. |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
SIRT3 is a member of the Sir2 family of NAD+-dependent protein deacetylases that promotes longevity in many organisms. The processed, short form of SIRT3 is a well-established mitochondrial protein whose deacetylase activity regulates various metabolic processes. However, the presence of full-length (FL) SIRT3 in the nucleus and its functional importance remains controversial. Our previous studies demonstrated that nuclear FL-SIRT3 functions as a histone deacetylase and is transcriptionally repressive when artificially recruited to a reporter gene. Here, we report that nuclear FL-SIRT3 is subjected to rapid degradation upon cellular stress, including oxidative stress and UV-irradiation, whereas the mitochondrial, processed form is unaffected. FL-SIRT3 degradation is mediated by the ubiquitin-proteasome pathway, at least partially through the E3 activity of SKP2. Finally, we show by chromatin immunoprecipitation that some target genes of nuclear SIRT3 are derepressed upon the degradation of SIRT3 caused by stress stimuli. Thus, SIRT3 exhibits a previously unappreciated role in the nucleus modulating the expression of some stress-related and nuclear-encoded mitochondrial genes.
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| |
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| Overall design |
ChIP-seq with a SIRT3 antibody in untreated, UV-irradiated, and stable SIRT3 knockdown (KD) U2OS cells
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| |
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| Contributor(s) |
Iwahara T, Reinberg D, Bonasio R |
| Citation(s) |
23045395 |
| |
| Submission date |
Sep 19, 2012 |
| Last update date |
Feb 04, 2022 |
| Contact name |
Roberto Bonasio |
| Organization name |
University of Pennsylvania
|
| Department |
Cell and Developmental Biology
|
| Lab |
Bonasio
|
| Street address |
3400 Civic Center Blvd - SCTR 9-111
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (8)
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| Relations |
| BioProject |
PRJNA175522 |
| SRA |
SRP015817 |
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