| Literature DB >> 32208170 |
Spencer A Haws1, Deyang Yu2, Cunqi Ye3, Coral K Wille4, Long C Nguyen5, Kimberly A Krautkramer1, Jay L Tomasiewicz6, Shany E Yang7, Blake R Miller7, Wallace H Liu1, Kazuhiko Igarashi8, Rupa Sridharan9, Benjamin P Tu3, Vincent L Cryns10, Dudley W Lamming11, John M Denu12.
Abstract
S-adenosylmethionine (SAM) is the methyl-donor substrate for DNA and histone methyltransferases that regulate epigenetic states and subsequent gene expression. This metabolism-epigenome link sensitizes chromatin methylation to altered SAM abundance, yet the mechanisms that allow organisms to adapt and protect epigenetic information during life-experienced fluctuations in SAM availability are unknown. We identified a robust response to SAM depletion that is highlighted by preferential cytoplasmic and nuclear mono-methylation of H3 Lys 9 (H3K9) at the expense of broad losses in histone di- and tri-methylation. Under SAM-depleted conditions, H3K9 mono-methylation preserves heterochromatin stability and supports global epigenetic persistence upon metabolic recovery. This unique chromatin response was robust across the mouse lifespan and correlated with improved metabolic health, supporting a significant role for epigenetic adaptation to SAM depletion in vivo. Together, these studies provide evidence for an adaptive response that enables epigenetic persistence to metabolic stress.Entities:
Keywords: SAM; aging; chromatin; epigenetics; histone; metabolism; methionine; methylation; persistence
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Year: 2020 PMID： 32208170 PMCID： PMC7191556 DOI： 10.1016/j.molcel.2020.03.004
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970