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Methyl-Metabolite Depletion Elicits Adaptive Responses to Support Heterochromatin Stability and Epigenetic Persistence.
Haws, Spencer A; Yu, Deyang; Ye, Cunqi; Wille, Coral K; Nguyen, Long C; Krautkramer, Kimberly A; Tomasiewicz, Jay L; Yang, Shany E; Miller, Blake R; Liu, Wallace H; Igarashi, Kazuhiko; Sridharan, Rupa; Tu, Benjamin P; Cryns, Vincent L; Lamming, Dudley W; Denu, John M.
Afiliação
  • Haws SA; Department of Biomolecular Chemistry, SMPH, University of Wisconsin-Madison, Madison, WI 53706, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
  • Yu D; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Department of Medicine, SMPH, University of Wisconsin-Madison, Madison, WI 53705, USA; Molecular & Environmental Toxicology Center, SMPH, University of Wisconsin-Madison, Madison, WI 53705, USA.
  • Ye C; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Wille CK; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
  • Nguyen LC; Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
  • Krautkramer KA; Department of Biomolecular Chemistry, SMPH, University of Wisconsin-Madison, Madison, WI 53706, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
  • Tomasiewicz JL; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
  • Yang SE; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Department of Medicine, SMPH, University of Wisconsin-Madison, Madison, WI 53705, USA.
  • Miller BR; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Department of Medicine, SMPH, University of Wisconsin-Madison, Madison, WI 53705, USA.
  • Liu WH; Department of Biomolecular Chemistry, SMPH, University of Wisconsin-Madison, Madison, WI 53706, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
  • Igarashi K; Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Center for Regulatory Epigenome and Diseases, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
  • Sridharan R; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA.
  • Tu BP; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Cryns VL; Department of Medicine, SMPH, University of Wisconsin-Madison, Madison, WI 53705, USA; Molecular & Environmental Toxicology Center, SMPH, University of Wisconsin-Madison, Madison, WI 53705, USA; University of Wisconsin Carbone Cancer Center, Madison, WI 53792, USA.
  • Lamming DW; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Department of Medicine, SMPH, University of Wisconsin-Madison, Madison, WI 53705, USA; Molecular & Environmental Toxicology Center, SMPH, University of Wisconsin-Madison, Madison, WI 53705, USA; University of Wisconsin Carb
  • Denu JM; Department of Biomolecular Chemistry, SMPH, University of Wisconsin-Madison, Madison, WI 53706, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA. Electronic address: john.denu@wisc.edu.
Mol Cell ; 78(2): 210-223.e8, 2020 04 16.
Article em En | MEDLINE | ID: mdl-32208170
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: S-Adenosilmetionina / Heterocromatina / Metilação de DNA / Metaboloma Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: S-Adenosilmetionina / Heterocromatina / Metilação de DNA / Metaboloma Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article