Methylation deficiency disrupts biological rhythms from bacteria to humans

Jean-Michel Fustin, Shiqi Ye, Christin Rakers, Kensuke Kaneko, Kazuki Fukumoto, Mayu Yamano, Marijke Versteven, Ellen Grünewald, Samantha J. Cargill, T. Katherine Tamai, Yao Xu, Maria Luísa Jabbur, Rika Kojima, Melisa L. Lamberti, Kumiko Yoshioka-Kobayashi, David Whitmore, Stephanie Tammam, P. Lynne Howell, Ryoichiro Kageyama, Takuya MatsuoRalf Stanewsky, Diego A. Golombek, Carl Hirschie Johnson, Hideaki Kakeya, Gerben van Ooijen, Hitoshi Okamura

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The methyl cycle is a universal metabolic pathway providing methyl groups for the methylation of nuclei acids and proteins, regulating all aspects of cellular physiology. We have previously shown that methyl cycle inhibition in mammals strongly affects circadian rhythms. Since the methyl cycle and circadian clocks have evolved early during evolution and operate in organisms across the tree of life, we sought to determine whether the link between the two is also conserved. Here, we show that methyl cycle inhibition affects biological rhythms in species ranging from unicellular algae to humans, separated by more than 1 billion years of evolution. In contrast, the cyanobacterial clock is resistant to methyl cycle inhibition, although we demonstrate that methylations themselves regulate circadian rhythms in this organism. Mammalian cells with a rewired bacteria-like methyl cycle are protected, like cyanobacteria, from methyl cycle inhibition, providing interesting new possibilities for the treatment of methylation deficiencies.
Original languageEnglish
Article number211
JournalCommunications Biology
Issue number1
Early online date6 May 2020
Publication statusPublished - 6 May 2020


  • Animals
  • Arabidopsis/physiology
  • Caenorhabditis elegans/physiology
  • Chlamydomonas reinhardtii/physiology
  • Chlorophyta/physiology
  • Circadian Rhythm
  • Drosophila melanogaster/physiology
  • Humans
  • Methylation
  • Mice/physiology
  • Synechococcus/physiology
  • Zebrafish/physiology


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