Histone H4 lysine 16 acetylation regulates cellular lifespan

Cells undergoing developmental processes are characterized by persistent non-genetic alterations in chromatin, termed epigenetic changes, represented by distinct patterns of DNA methylation and histone post-translational modifications. Sirtuins, a group of conserved NAD+-dependent deacetylases or AD...

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Veröffentlicht in:Nature (London) Jg. 459; H. 7248; S. 802 - 807
Hauptverfasser: Dang, Weiwei, Steffen, Kristan K, Perry, Rocco, Dorsey, Jean A, Johnson, F. Brad, Shilatifard, Ali, Kaeberlein, Matt, Kennedy, Brian K, Berger, Shelley L
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 11.06.2009
Nature Publishing Group
Schlagworte:
Acetylation
Acetyltransferases
Acetyltransferases - metabolism
Adenosine diphosphate
Ageing, cell death
Aging
antagonists & inhibitors
Apoptosis
Binding sites
Biological and medical sciences
Causes of
Cell Division
Cell physiology
Cells
Changes
chemistry
Chromatin
Chromatin - genetics
Chromatin - metabolism
cytology
deficiency
Epistasis, Genetic
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Fungal
Gene Silencing
Genetics
Health aspects
Histone Acetyltransferases
Histone Deacetylase Inhibitors
Histone Deacetylases
Histone Deacetylases - deficiency
Histone Deacetylases - metabolism
histones
Histones - chemistry
Histones - genetics
Histones - metabolism
Humanities and Social Sciences
Life span
lysine
Lysine - metabolism
metabolism
Methylation
Molecular and cellular biology
multidisciplinary
Mutant Proteins
Mutant Proteins - genetics
Mutant Proteins - metabolism
Mutation
Physiological aspects
Post-translational modification
Proteins
Ribosomal DNA
Saccharomyces cerevisiae
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins
Saccharomyces cerevisiae Proteins - metabolism
Science
Science (multidisciplinary)
senescence
Silent Information Regulator Proteins, Saccharomyces cerevisiae
Silent Information Regulator Proteins, Saccharomyces cerevisiae - antagonists & inhibitors
Silent Information Regulator Proteins, Saccharomyces cerevisiae - deficiency
Silent Information Regulator Proteins, Saccharomyces cerevisiae - metabolism
Sirtuin 2
Sirtuins
Sirtuins - antagonists & inhibitors
Sirtuins - deficiency
Sirtuins - metabolism
Studies
Telomere
Telomere - genetics
Telomere - metabolism
transcription (genetics)
Transcription, Genetic
Yeasts
United States
Ascomycota
Chromatin
Yeast
Longevity
Fungi
Histone H4
Gene silencing
Regulation(control)
Lysine
Cell component
Epigenetics
Acetylation
Saccharomyces cerevisiae
ISSN:0028-0836, 1476-4687, 1476-4687
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Zusammenfassung:Cells undergoing developmental processes are characterized by persistent non-genetic alterations in chromatin, termed epigenetic changes, represented by distinct patterns of DNA methylation and histone post-translational modifications. Sirtuins, a group of conserved NAD+-dependent deacetylases or ADP-ribosyltransferases, promote longevity in diverse organisms; however, their molecular mechanisms in ageing regulation remain poorly understood. Yeast Sir2, the first member of the family to be found, establishes and maintains chromatin silencing by removing histone H4 lysine 16 acetylation and bringing in other silencing proteins. Here we report an age-associated decrease in Sir2 protein abundance accompanied by an increase in H4 lysine 16 acetylation and loss of histones at specific subtelomeric regions in replicatively old yeast cells, which results in compromised transcriptional silencing at these loci. Antagonizing activities of Sir2 and Sas2, a histone acetyltransferase, regulate the replicative lifespan through histone H4 lysine 16 at subtelomeric regions. This pathway, distinct from existing ageing models for yeast, may represent an evolutionarily conserved function of sirtuins in regulation of replicative ageing by maintenance of intact telomeric chromatin.
Bibliographie:http://dx.doi.org/10.1038/nature08085
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Author Contributions Project planning was performed by W.D., F.B.J., A.S., B.K.K., S.L.B; experimental work by W.D., K.K.S., R.P., J.D.; data analysis by W.D.,K.K.S., F.B.J., M.K.,B.K.K.,S.L.B.; manuscript composition by W.D., F.B.J., M.K., B.K.K., and S.L.B.
ISSN:0028-0836
1476-4687
1476-4687
DOI:10.1038/nature08085