Histone H4 lysine-16 acetylation regulates cellular lifespan

By Weiwei Dang, Kristan K. Steffen, Rocco Perry, Jean A. Dorsey, F. Johnson, A. Shilatifard, Matt Kaeberlein, Brian K. Kennedy, Shelley L. Berger. Nature, 2009

643 citations recorded by the source corpus.

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.

Subfields: Aging, Geriatrics and Gerontology, Plant Science

View Paper: https://www.semanticscholar.org/paper/f75e9ed765045a92661909b00883359f2abcbfd1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Aging

1. J. Tyler
2. Guido Kroemer
3. Guillermo Mariño
4. Craig B. Thompson
5. Sangita Pal
6. Chao Lu
7. D. Rubinsztein

In Geriatrics and Gerontology

1. Guido Kroemer
2. Craig B. Thompson
3. Chao Lu

In Plant Science

1. Guido Kroemer
2. Guillermo Mariño
3. Craig B. Thompson
4. Beth Levine
5. Douglas R. Green

Citations in the corpus

• Epigenetics and aging (2016, background): “In contrast to the reduced levels ofH3K56Acduring aging, the levels of H4 K16Ac increase during yeast replicative aging (46).”
• Metabolic regulation of epigenetics (2012, background): “Indeed, metabolomic and biochemical analysis revealed that mutant IDHs display a neomorphic activity of producing 2-hydroxyglutarate (2HG) from aKG (Dang et al., 2009a; Ward et al., 2010).”
• Replicative and Chronological Aging in Saccharomyces cerevisiae (2012, neutral): “Detailed written and video protocols have been published on how this assay is performed in the Kaeberlein and Kennedy labs, and we refer interested readers to these (Kaeberlein and Kennedy, 2005; Steffen et al., 2009).”
• Autophagy and aging. (2011, background): “An H4 K16Q mutation (which mimics deacetylation) suffices to increase life span (Dang et al., 2009).”