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The Set7 Lysine Methyltransferase Regulates Plasticity in Oxidative Phosphorylation Necessary for Trained Immunity Induced by β-Glucan

  • Keating, Samuel T.1
  • Groh, Laszlo1
  • van der Heijden, Charlotte D.C.C.1
  • Rodriguez, Hanah2
  • dos Santos, Jéssica C.1
  • Fanucchi, Stephanie3, 4
  • Okabe, Jun2
  • Kaipananickal, Harikrishnan2, 5
  • van Puffelen, Jelmer H.1, 6
  • Helder, Leonie1
  • Noz, Marlies P.1
  • Matzaraki, Vasiliki1
  • Li, Yang1, 7
  • de Bree, L. Charlotte J.1, 8, 9
  • Koeken, Valerie A.C.M.1
  • Moorlag, Simone J.C.F.M.1
  • Mourits, Vera P.1
  • Domínguez-Andrés, Jorge1
  • Oosting, Marije1
  • Bulthuis, Elianne P.10
  • And 6 more
  • 1 Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, the Netherlands
  • 2 Epigenetics in Human Health and Disease, Department of Diabetes, Monash University, Melbourne, VIC, Australia
  • 3 Division of Chemical, Systems and Synthetic Biology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
  • 4 Gene Expression and Biophysics Group, CSIR Biosciences, Pretoria, South Africa
  • 5 Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC, Australia
  • 6 Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands
  • 7 Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine, Helmholtz Centre for Infection Research, Hannover Medical School, 30625 Hannover, Germany
  • 8 Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark
  • 9 Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, Odense, Denmark
  • 10 Department of Biochemistry, Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, the Netherlands
  • 11 Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong City, Hong Kong SAR
  • 12 Department of Medical Genetics, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
  • 13 Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany
Published Article
Cell Reports
Publication Date
Apr 21, 2020
DOI: 10.1016/j.celrep.2020.107548
PMID: 32320649
PMCID: PMC7184679
PubMed Central


Using a combination of pharmacological and genetic approaches, Keating et al. show that the Set7 methyltransferase is a regulator of trained immunity induced by β-glucan. Activation of Set7 increases oxidative phosphorylation in trained cells via histone lysine methylation at gene enhancers of key enzymes of the TCA cycle.

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