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Histone H4 lysine‐16 acetylation regulates cellular lifespan
Author(s) -
Dang Weiwei,
Steffen Kristan K,
Kaeberlein Matt,
Kennedy Brian K,
Berger Shelley
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.662.2
Subject(s) - histone h4 , biology , acetylation , chromatin , histone , histone acetyltransferase , epigenetics , histone methyltransferase , microbiology and biotechnology , subtelomere , histone code , genetics , gene silencing , chromatin remodeling , lysine , histone h3 , histone h2a , histone modifying enzymes , telomere , nucleosome , dna , gene , amino acid
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‐ribosylases, promote longevity in diverse organisms; however, their molecular mechanisms in aging regulation remain poorly understood. Yeast Sir2, the founding member of the family, establishes and maintains chromatin silencing by removing H4 lysine 16 acetylation and bringing in other silencing proteins. Here we show 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 yeast aging models and the role of Sir2 in controlling the accumulation of extra‐chromosomal rDNA circles (ERCs) during aging, may represent an evolutionarily conserved function of Sirtuins in regulation of replicative aging by maintenance of intact telomeric chromatin.