Reversible DNA methylation regulates seasonal photoperiodic time measurement

Stevenson, T.J. and Prendergast, B.J. (2013) Reversible DNA methylation regulates seasonal photoperiodic time measurement. Proceedings of the National Academy of Sciences of the United States of America, 110(41), pp. 16651-16656. (doi: 10.1073/pnas.1310643110) (PMID:24067648) (PMCID:PMC3799317)

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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.

Item Type:Articles
Additional Information:This project was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) (Grant UL1 RR024999). This work was funded by NIH/National Institute of Allergy and Infectious Diseases Grant AI-67406.
Glasgow Author(s) Enlighten ID:Stevenson, Dr Tyler
Authors: Stevenson, T.J., and Prendergast, B.J.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN (Online):1091-6490

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