The Metabolic Impact on Histone Acetylation and Transcription in Ageing

Peleg, Shahaf; Feller, Christian; Ladurner, Andreas G.; Imhof, Axel

doi:10.1016/j.tibs.2016.05.008

Cited by 151 publications

(123 citation statements)

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“…It is becoming evident that histone acetylation plays a more nuanced role in gene regulation, with site specific changes in histone acetylation playing just as important a role as more global alterations (Peleg et al, 2016). It is notable that lifespan increases associated with treatment with histone deacetylase inhibitors (HDACi's) such as trichostatin A (TSA) and butyrate often show more targeted gene-specific effects (Tao et al, 2004;Walsh et al, 2015).…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Targeting chromatin aging - The epigenetic impact of longevity-associated interventions

Field

Adams

2017

Experimental Gerontology

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Section: Accepted M Manuscriptmentioning

confidence: 99%

Targeting chromatin aging - The epigenetic impact of longevity-associated interventions

Field

Adams

2017

Experimental Gerontology

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“…Such disturbance may lead to human diseases, including cancer, 28 inflammatory diseases, 29 Huntington’s disease, 30 and aging-associated diseases. 31 …”

mentioning

confidence: 99%

Nucleosome Histone Tail Conformation and Dynamics: Impacts of Lysine Acetylation and a Nearby Minor Groove Benzo[a]pyrene-Derived Lesion

Fu¹,

Cai²,

Geacintov³

et al. 2017

Biochemistry

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Histone tails in nucleosomes play critical roles in regulation of many biological processes including chromatin compaction, transcription and DNA repair. Moreover, post-translational modifications, notably lysine acetylation, are crucial to these functions. While the tails have been intensively studied, how the structures and dynamics of tails are impacted by the presence of a nearby bulky DNA lesion is a frontier research area, and how these properties are impacted by tail lysine acetylation remains unexplored. To obtain molecular insight, we have utilized all atom 3 μs molecular dynamics simulations of nucleosome core particles (NCPs) to determine the impact of a nearby DNA lesion, 10S (+)-trans-anti-B[a]P-N2-dG--the major adduct derived from the procarcinogen benzo[a]pyrene--on H2B tail behavior in unacetylated and acetylated states. We similarly studied lesion-free NCPs to investigate the normal properties of the H2B tail in both states. In the lesion-free NCPs, the charge-neutralization upon lysine acetylation causes release of the tail from the DNA. When the lesion is present, it stably engulfs part of the nearby tail, impairing the interactions between DNA and tail. With the tail in an acetylated state, the lesion still interacts with part of it, although unstably. The lesion’s partial entrapment of the tail should hinder the tail from interacting with other nucleosomes, and other proteins such as acetylases, deacetylases and acetyl-lysine binding proteins, and thus disrupt critical tail-governed processes. Hence, the lesion would impede tail functions modulated by acetylation or deacetylation, causing aberrant chromatin structures and impaired biological transactions such as transcription and DNA repair.

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“…The close connection between metabolism and epigenetic processes was also illustrated in a study presented by Axel Imhof (LudwigMaximilians University), who showed that the attenuation of an age-dependent increase in lysine acetylation results in lifespan extension in fruit flies 12 .…”

Section: Competing Financial Interestsmentioning

confidence: 84%