Circadian behavior is light-reprogrammed by plastic DNA methylation

Nat Neurosci. 2014 Mar;17(3):377-82. doi: 10.1038/nn.3651. Epub 2014 Feb 16.


The timing of daily circadian behavior can be highly variable among different individuals, and twin studies have suggested that about half of this variability is environmentally controlled. Similar plasticity can be seen in mice exposed to an altered lighting environment, for example, 22-h instead of 24-h, which stably alters the genetically determined period of circadian behavior for months. The mechanisms mediating these environmental influences are unknown. We found that transient exposure of mice to such lighting stably altered global transcription in the suprachiasmatic nucleus (SCN) of the hypothalamus (the master clock tissue regulating circadian behavior in mammals). In parallel, genome-wide methylation profiling revealed global alterations in promoter DNA methylation in the SCN that correlated with these changes. Behavioral, transcriptional and DNA methylation changes were reversible after prolonged re-entrainment to 24-h d. Notably, infusion of a methyltransferase inhibitor to the SCN suppressed period changes. We conclude that the SCN utilizes DNA methylation as a mechanism to drive circadian clock plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actigraphy
  • Animals
  • Behavior, Animal / physiology
  • Circadian Rhythm / genetics*
  • Circadian Rhythm Signaling Peptides and Proteins / genetics*
  • Circadian Rhythm Signaling Peptides and Proteins / metabolism*
  • DNA Methylation / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity / physiology*
  • Photoperiod*
  • Suprachiasmatic Nucleus / metabolism
  • Transcriptome / genetics


  • Circadian Rhythm Signaling Peptides and Proteins

Associated data

  • GEO/GSE54021
  • GEO/GSE54124