Methylation deficiency disrupts biological rhythms from bacteria to humans

Fustin, Jean Michel, Ye, Shiqi, Rakers, Christin, Kaneko, Kensuke, Fukumoto, Kazuki, Yamano, Mayu, Versteven, Marijke, Grünewald, Ellen, Cargill, Samantha J., Tamai, T. Katherine, Xu, Yao, Jabbur, Maria Luísa, Kojima, Rika, Lamberti, Melisa L., Yoshioka-Kobayashi, Kumiko, Whitmore, David, Tammam, Stephanie, Howell, P. Lynne, Kageyama, Ryoichiro, Matsuo, Takuya, Stanewsky, Ralf, Golombek, Diego A., Johnson, Carl Hirschie, Kakeya, Hideaki, van Ooijen, Gerben, and Okamura, Hitoshi (2020) Methylation deficiency disrupts biological rhythms from bacteria to humans. Communications Biology, 3 (1). 211.

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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.

Item ID: 75322
Item Type: Article (Research - C1)
ISSN: 2399-3642
Copyright Information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Date Deposited: 11 Aug 2022 00:27
FoR Codes: 31 BIOLOGICAL SCIENCES > 3109 Zoology > 310909 Animal physiology - cell @ 100%
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