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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Haws SA,Yu D,Ye C,Wille CK,Nguyen LC,Krautkramer KA,Tomasiewicz JL,Yang SE,Miller BR,Liu WH,Igarashi K,Sridharan R,Tu BP,Cryns VL,Lamming DW,Denu JMdoi
10.1016/j.molcel.2020.03.004subject
Has Abstractpub_date
2020-04-16 00:00:00pages
210-223.e8issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(20)30152-0journal_volume
78pub_type
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