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The contribution of active and passive mechanisms of 5mC and 5hmC removal in human T lymphocytes is differentiation- and activation-dependent

  • Vincenzetti, Lucia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Leoni, Cristina Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Chirichella, Michele Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Kwee, Ivo Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Monticelli, Silvia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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    30.01.2019
Published in:
  • European Journal of Immunology. - 2019, p. 1-15
DNA methylation
Epigenetics
T lymphocytes
Differentiation
Activation
English In mammals, the 5’-methylcytosine (5mC) modification in the genomic DNA contributes to the dynamic control of gene expression. 5mC erasure is required for the activation of developmental programs and occurs either by passive dilution through DNA replication, or by enzymatic oxidation of the methyl mark to 5-hydroxymethylcytosine (5hmC), which can persist as such or undergo further oxidation and enzymatic removal. The relative contribution of each mechanism to epigenetic control in dynamic biological systems still remains a compelling question. To explore this critical issue, we used primary human T lymphocytes, in which two cellular states can be clearly identified, namely quiescent naïve T cells, which are slowly or rarely proliferating, and rapidly proliferating activated T cells. We found that active mechanisms of methylation removal were selectively at work in naïve T cells, while memory T lymphocytes entirely relied on passive, replication-dependent dilution, suggesting that proliferative capacity influences the choice of the preferential demethylation mechanism. Active processes of demethylation appear to be critical in quiescent naïve T lymphocytes for the maintenance of regulatory regions poised for rapid responses to physiological stimuli.
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  • English
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Medicine
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https://n2t.net/ark:/12658/srd1318874
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