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Epigenetic regulation by DNA methyltransferases during torpor in the thirteen-lined ground squirrel Ictidomys tridecemlineatus

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Abstract

The thirteen-lined ground squirrel, Ictidomys tridecemlineatus, is a mammal capable of lowering its Tb to almost 0 °C while undergoing deep torpor bouts over the winter. To decrease its metabolic rate to such a drastic extent, the squirrel must undergo multiple physiological, biological, and molecular alterations including downregulation of almost all nonessential processes. Epigenetic regulation allows for a dynamic range of transient phenotypes, allowing the squirrel to downregulate energy-expensive and nonessential pathways during torpor. DNA methylation is a prominent form of epigenetic regulation; therefore, the DNA methyltransferase (DNMT) family of enzymes were studied by measuring expression and activity levels of the five major proteins during torpor bouts. Additionally, specific cytosine marks on genomic DNA were quantified to further elucidate DNA methylation during hibernation. A tissue-specific response was observed that highlighted variant degrees of DNA methylation and DNMT expression/activity, demonstrating that DNA methylation is a highly complex form of epigenetic regulation and likely one of many regulatory mechanisms that enables metabolic rate depression in response to torpor.

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Acknowledgements

This work is supported by a discovery grant from the Natural Science and Engineering Research Council of Canada (#6793) awarded to KBS. KBS holds the Canada Research Chair in Molecular Physiology. SNT held a NSERC postgraduate scholarship. Thanks also to Hanane Hadj-Moussa for guidance on the preparation of the manuscript.

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  1. Shannon N. Tessier

    Present address: BioMEMS Resource Center & Center for Engineering in Medicine, Massachusetts General Hospital & Harvard Medical School, 114 16th Street, Charlestown, MA, 02129, USA

Authors and Affiliations

  1. Institute of Biochemistry and Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada

    Shannon N. Tessier, W. Aline Ingelson-Filpula & Kenneth B. Storey

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  1. Shannon N. Tessier
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  2. W. Aline Ingelson-Filpula
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  3. Kenneth B. Storey
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SNT and KBS conceptualized and designed the project and SNT conducted all experiments. Data analysis and assembly of the manuscript were carried out by AIF, SNT, and KBS.

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Correspondence to Kenneth B. Storey.

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Tessier, S.N., Ingelson-Filpula, W.A. & Storey, K.B. Epigenetic regulation by DNA methyltransferases during torpor in the thirteen-lined ground squirrel Ictidomys tridecemlineatus. Mol Cell Biochem 476, 3975–3985 (2021). https://doi.org/10.1007/s11010-021-04214-1

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