Cargando…

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

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 lifespa...

Descripción completa

Detalles Bibliográficos
Autores principales: Molina‐Serrano, Diego, Schiza, Vassia, Demosthenous, Christis, Stavrou, Emmanouil, Oppelt, Jan, Kyriakou, Dimitris, Liu, Wei, Zisser, Gertrude, Bergler, Helmut, Dang, Weiwei, Kirmizis, Antonis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167350/
https://www.ncbi.nlm.nih.gov/pubmed/27799288
http://dx.doi.org/10.15252/embr.201642540
_version_ 1782483163822424064
author Molina‐Serrano, Diego
Schiza, Vassia
Demosthenous, Christis
Stavrou, Emmanouil
Oppelt, Jan
Kyriakou, Dimitris
Liu, Wei
Zisser, Gertrude
Bergler, Helmut
Dang, Weiwei
Kirmizis, Antonis
author_facet Molina‐Serrano, Diego
Schiza, Vassia
Demosthenous, Christis
Stavrou, Emmanouil
Oppelt, Jan
Kyriakou, Dimitris
Liu, Wei
Zisser, Gertrude
Bergler, Helmut
Dang, Weiwei
Kirmizis, Antonis
author_sort Molina‐Serrano, Diego
collection PubMed
description 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 lifespan mediated by CR, and (iii) transcriptome analysis indicates that nat4Δ largely mimics the effects of CR, especially in the induction of stress‐response genes. We further show that nicotinamidase Pnc1, which is typically upregulated under CR, is required for nat4Δ‐mediated longevity. Collectively, these findings establish histone N‐acH4 as a regulator of cellular lifespan that links CR to increased stress resistance and longevity.
format Online
Article
Text
id pubmed-5167350
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-51673502016-12-28 Loss of Nat4 and its associated histone H4 N‐terminal acetylation mediates calorie restriction‐induced longevity Molina‐Serrano, Diego Schiza, Vassia Demosthenous, Christis Stavrou, Emmanouil Oppelt, Jan Kyriakou, Dimitris Liu, Wei Zisser, Gertrude Bergler, Helmut Dang, Weiwei Kirmizis, Antonis EMBO Rep Articles 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 lifespan mediated by CR, and (iii) transcriptome analysis indicates that nat4Δ largely mimics the effects of CR, especially in the induction of stress‐response genes. We further show that nicotinamidase Pnc1, which is typically upregulated under CR, is required for nat4Δ‐mediated longevity. Collectively, these findings establish histone N‐acH4 as a regulator of cellular lifespan that links CR to increased stress resistance and longevity. John Wiley and Sons Inc. 2016-10-31 2016-12 /pmc/articles/PMC5167350/ /pubmed/27799288 http://dx.doi.org/10.15252/embr.201642540 Text en © 2016 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Molina‐Serrano, Diego
Schiza, Vassia
Demosthenous, Christis
Stavrou, Emmanouil
Oppelt, Jan
Kyriakou, Dimitris
Liu, Wei
Zisser, Gertrude
Bergler, Helmut
Dang, Weiwei
Kirmizis, Antonis
Loss of Nat4 and its associated histone H4 N‐terminal acetylation mediates calorie restriction‐induced longevity
title Loss of Nat4 and its associated histone H4 N‐terminal acetylation mediates calorie restriction‐induced longevity
title_full Loss of Nat4 and its associated histone H4 N‐terminal acetylation mediates calorie restriction‐induced longevity
title_fullStr Loss of Nat4 and its associated histone H4 N‐terminal acetylation mediates calorie restriction‐induced longevity
title_full_unstemmed Loss of Nat4 and its associated histone H4 N‐terminal acetylation mediates calorie restriction‐induced longevity
title_short Loss of Nat4 and its associated histone H4 N‐terminal acetylation mediates calorie restriction‐induced longevity
title_sort loss of nat4 and its associated histone h4 n‐terminal acetylation mediates calorie restriction‐induced longevity
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167350/
https://www.ncbi.nlm.nih.gov/pubmed/27799288
http://dx.doi.org/10.15252/embr.201642540
work_keys_str_mv AT molinaserranodiego lossofnat4anditsassociatedhistoneh4nterminalacetylationmediatescalorierestrictioninducedlongevity
AT schizavassia lossofnat4anditsassociatedhistoneh4nterminalacetylationmediatescalorierestrictioninducedlongevity
AT demosthenouschristis lossofnat4anditsassociatedhistoneh4nterminalacetylationmediatescalorierestrictioninducedlongevity
AT stavrouemmanouil lossofnat4anditsassociatedhistoneh4nterminalacetylationmediatescalorierestrictioninducedlongevity
AT oppeltjan lossofnat4anditsassociatedhistoneh4nterminalacetylationmediatescalorierestrictioninducedlongevity
AT kyriakoudimitris lossofnat4anditsassociatedhistoneh4nterminalacetylationmediatescalorierestrictioninducedlongevity
AT liuwei lossofnat4anditsassociatedhistoneh4nterminalacetylationmediatescalorierestrictioninducedlongevity
AT zissergertrude lossofnat4anditsassociatedhistoneh4nterminalacetylationmediatescalorierestrictioninducedlongevity
AT berglerhelmut lossofnat4anditsassociatedhistoneh4nterminalacetylationmediatescalorierestrictioninducedlongevity
AT dangweiwei lossofnat4anditsassociatedhistoneh4nterminalacetylationmediatescalorierestrictioninducedlongevity
AT kirmizisantonis lossofnat4anditsassociatedhistoneh4nterminalacetylationmediatescalorierestrictioninducedlongevity