Cytosine modifications exhibit circadian oscillations that are involved in epigenetic diversity and aging

  • Nat Commun. 2018 Feb 13;9(1):644. doi: 10.1038/s41467-018-03073-7.
Gabriel Oh  1 ,  Sasha Ebrahimi  1 ,  Matthew Carlucci  1 ,  Aiping Zhang  1 ,  Akhil Nair  1 ,  Daniel E Groot  1 ,  Viviane Labrie  1  2 ,  Peixin Jia  1 ,  Edward S Oh  1 ,  Richie H Jeremian  1 ,  Miki Susic  1 ,  Tenjin C Shrestha  3  4 ,  Martin R Ralph  4 ,  Juozas Gordevičius  5  6 ,  Karolis Koncevičius  5  6 ,  Art Petronis  7  8
Affiliations
  • 1. The Krembil Family Epigenetics Laboratory, The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8, Canada.
  • 2. Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, 49503, USA.
  • 3. Department of Cell and Systems Biology, University of Toronto, Toronto, ON, M5S 3G5, Canada.
  • 4. Department of Psychology, University of Toronto, Toronto, ON, M5S 3G5, Canada.
  • 5. Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, LT-10257, Lithuania.
  • 6. Institute of Data Science and Digital Technologies, Vilnius University, Vilnius, LT-08663, Lithuania.
  • 7. The Krembil Family Epigenetics Laboratory, The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8, Canada. [email protected].
  • 8. Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, LT-10257, Lithuania. [email protected].
PMID: 29440637 DOI: 10.1038/s41467-018-03073-7
Abstract

Circadian rhythmicity governs a remarkable array of fundamental biological functions and is mediated by cyclical transcriptomic and proteomic activities. Epigenetic factors are also involved in this circadian machinery; however, despite extensive efforts, detection and characterization of circadian cytosine modifications at the nucleotide level have remained elusive. In this study, we report that a large proportion of epigenetically variable cytosines show a circadian pattern in their modification status in mice. Importantly, the cytosines with circadian epigenetic oscillations significantly overlap with the cytosines exhibiting age-related changes in their modification status. Our findings suggest that evolutionary advantageous processes such as circadian rhythmicity can also contribute to an organism's deterioration.

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