Loss of Nat4 and its associated histone H4 N-terminal acetylation mediates calorie restriction-induced longevity.

ABSTRACT: Changes in histone modifications are an attractive model through which environmental signals, such as diet, could be integrated in the cell for regulating its lifespan. However, evidence linking dietary interventions with specific alterations in histone modifications that subsequently affect lifespan remains elusive. We show here that deletion of histone N-alpha-terminal acetyltransferase Nat4 and loss of its associated H4 N-terminal acetylation (N-acH4) extend yeast replicative lifespan. Notably, nat4Δ-induced longevity is epistatic to the effects of calorie restriction (CR). Consistent with this, (i) Nat4 expression is downregulated and the levels of N-acH4 within chromatin are reduced upon CR, (ii) constitutive expression of Nat4 and maintenance of N-acH4 levels reduces the extension of

SUBMITTER: Molina-Serrano D 

PROVIDER: S-EPMC5167350 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature