Informace o publikaci
Loss Of Histone N-terminal Acetylation Mimics Calorie Restriction-Induced Longevity
| Název česky | Ztráta N-terminální acetylace histonu napodobuje dlouhověkost indukovanou omezením kalorií |
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| Autoři | |
| Rok publikování | 2015 |
| Druh | Další prezentace na konferencích |
| Citace | |
| Popis | Post-translation modifications of histones control key DNA-based processes like transcription. Typically, these modifications are deposited on the side chains of the histone amino-acids. We have previously characterized the function of a unique modification that is added at the N-terminal amino group of histones, namely N-alpha-terminal acetylation. Specifically, we have shown that when this modification is deposited on the N-terminus of histone H4 (N-acH4) by the acetyltransferase Nat4 it blocks methylation of the adjacent arginine 3 (H4R3) and consequently, facilitates transcriptional activation of the ribosomal DNA region. To further explore the biological role of Nat4, a global gene expression analysis was recently performed, revealing that deletion of Nat4 induces several stress-response genes that are also specifically activated in cells grown under calorie restriction (CR) conditions. Since CR extends replicative lifespan in yeast we then examined the effect of Nat4 deletion on longevity. Interestingly, we found that Nat4-deletion extends cellular lifespan to similar levels as CR. Importantly, deletion of Nat4 in combination with CR does not have an additive effect on longevity implying an epistatic effect. Furthermore, the extension in longevity upon Nat4 deletion is mediated by loss of H4 N-terminal acetylation since loss of this modification by mutating histone H4 serine 1 to aspartate (H4S1D) results in increased lifespan. Consistent with this, we also found that absence of H4R3 methylation, which is the antagonistic mark to N-acH4, by mutating arginine 3 to lysine (H4R3K) has the opposite effect on cellular lifespan. Overall, during this presentation a novel role for Nat4 and histone N-terminal acetylation in cellular lifespan will be described and a putative mechanism underlying this role will be proposed |