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| Status |
Public on Dec 12, 2018 |
| Title |
SIRT7-dependent deacetylation of fibrillarin controls H2A methylation and rRNA synthesis during the cell cycle |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| Summary |
Fibrillarin (FBL) is a dual function nucleolar protein which catalyses 2ยด-O methylation of pre-rRNA and methylation of histone H2A at glutamine 104 (H2AQ104me). The mechanisms that regulate FBL activity are unexplored. Here we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7. While reversible acetylation does not impact FBL-mediated pre-rRNA methylation, hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromsing H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. At the onset of mitosis, nucleolar disassembly is accompanied by hyperacetylation of FBL, loss of H2AQ104me and repression of Pol I transcription. H2AQ104me and transcriptional activity are restored by overexpression of an acetylation-deficient but not by an acetylation-mimicking FBL mutant. The results reveal that SIRT7-dependent deacetylation impacts nucleolar activity by a FBL-driven circuitry that mediates cell cycle-dependent fluctuation of rDNA transcription.
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| Overall design |
A total of 17 libraires analyzed divided on 6 experimental conditions, where 5 are made in triplicates, and one in duplicates.
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| Contributor(s) |
Iyer-Bierhoff A, Krogh N, Tessarz P, Ruppert T, Nielsen H, Grummt I |
| Citation(s) |
30540930 |
| Submission date |
Jun 05, 2018 |
| Last update date |
Mar 13, 2019 |
| Contact name |
Nicolai Krogh |
| E-mail(s) |
nicolaikj@sund.ku.dk
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| Organization name |
University of Copenhagen
|
| Department |
Department of Cellular and Molecular Medicine
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| Lab |
RNA Group - Prof. Henrik Nielsen
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| Street address |
Blegdamsvej 3B
|
| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
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| Platforms (1) |
| GPL17303 |
Ion Torrent Proton (Homo sapiens) |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA474692 |
| SRA |
SRP149808 |
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