Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 41, Pages 16651-16656Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1310643110
Keywords
biological rhythms; photoperiodism
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Funding
- National Center for Research Resources
- National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) [UL1 RR024999]
- NIH/National Institute of Allergy and Infectious Diseases Grant [AI-67406]
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In seasonally breeding vertebrates, changes in day length induce categorically distinct behavioral and reproductive phenotypes via thyroid hormone-dependent mechanisms. Winter photoperiods inhibit reproductive neuroendocrine function but cannot sustain this inhibition beyond 6 mo, ensuring vernal reproductive recrudescence. This genomic plasticity suggests a role for epigenetics in the establishment of seasonal reproductive phenotypes. Here, we report that DNA methylation of the proximal promoter for the type III deiodinase (dio3) gene in the hamster hypothalamus is reversible and critical for photoperiodic time measurement. Short photoperiods and winter-like melatonin inhibited hypothalamic DNA methyltransferase expression and reduced dio3 promoter DNA methylation, which up-regulated dio3 expression and induced gonadal regression. Hypermethylation attenuated reproductive responses to short photoperiods. Vernal refractoriness to short photoperiods reestablished summer-like methylation of the dio3 promoter, dio3 expression, and reproductive competence, revealing a dynamic and reversible mechanism of DNA methylation in the mammalian brain that plays a central role in physiological orientation in time.
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