bims-meprid Biomed News
on Metabolic-dependent epigenetic reprogramming in differentiation and disease
Issue of 2021‒06‒20
four papers selected by
Alessandro Carrer
Veneto Institute of Molecular Medicine

  1. Nat Metab. 2021 Jun 17.
      Global histone acetylation varies with changes in the nutrient and cell cycle phases; however, the mechanisms connecting these variations are not fully understood. Herein, we report that nutrient-related and cell-cycle-regulated nuclear acetate regulates global histone acetylation. Histone deacetylation-generated acetate accumulates in the nucleus and induces histone hyperacetylation. The nuclear acetate levels were controlled by glycolytic enzyme triosephosphate isomerase 1 (TPI1). Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. CDK2 accumulates in the cytosol during the late G1/S phases. Inactivation or blockade of nuclear translocation of TPI1 abrogates nutrient-dependent and cell-cycle-dependent global histone acetylation, chromatin condensation, gene transcription and DNA replication. These results identify the mechanism of maintaining global histone acetylation by nutrient and cell cycle signals.
  2. Biol Reprod. 2021 Jun 16. pii: ioab118. [Epub ahead of print]
      Metabolites control epigenetic mechanisms and, conversly, cell metabolism is regulated at the epigenetic level in response to changes in the cellular environnement. In recent years, this metabolo-epigenetic control of gene expression has been implicated in the regulation of multiple stages of embryonic development. The developmental potency of stem cells and their embryonic counterparts is directly determined by metabolic rewiring. Here, we review the current knowledge on the interplay between epigenetics and metabolism in the specific context of early germ cells development. We further develop the implications of metabolic rewiring in primordial germ cells in light of their epigenetic remodelling during cell fate determination. Finally, we discuss the relevance of concerted metabolic and epigenetic regulation of primordial germ cells in the context of mammalian transgenerational epigenetic inheritance.
    Keywords:  Epigenetics; Metabolism; Primordial Germ Cells; alpha-ketoglutarate
  3. Nat Metab. 2021 Jun 14.
      Pre-operative exercise therapy improves outcomes for many patients who undergo surgery. Despite the well-known effects on tolerance to systemic perturbation, the mechanisms by which pre-operative exercise protects the organ that is operated on from inflammatory injury are unclear. Here, we show that four-week aerobic pre-operative exercise significantly attenuates liver injury and inflammation from ischaemia and reperfusion in mice. Remarkably, these beneficial effects last for seven more days after completing pre-operative exercising. We find that exercise specifically drives Kupffer cells toward an anti-inflammatory phenotype with trained immunity via metabolic reprogramming. Mechanistically, exercise-induced HMGB1 release enhances itaconate metabolism in the tricarboxylic acid cycle that impacts Kupffer cells in an NRF2-dependent manner. Therefore, these metabolites and cellular/molecular targets can be investigated as potential exercise-mimicking pharmaceutical candidates to protect against liver injury during surgery.
  4. Neurochem Int. 2021 Jun 13. pii: S0197-0186(21)00145-5. [Epub ahead of print] 105099
      Humans have known for millennia that nutrition has a profound influence on health and disease, but it is only recently that we have begun mapping the mechanisms via which the dietary environment impacts brain physiology and behavior. Here we review recent evidence on the effects of high nutrient and methionine diets on neural epigenetic marks, gene expression, and behavior in invertebrate and vertebrate model organisms. We also discuss limitations, open questions, and future directions in the emerging field of the neuroepigenetics of nutrition.
    Keywords:  Behavior; dietary methionine; epigenetics; high fat diet; high sugar diet; metabolism; obesity