Abstract
Trachemys scripta elegans can survive up to three months of absolute anoxia at 3 °C and recover with minimal cellular damage. Red-eared sliders employ various physiological and biochemical adaptations to survive anoxia with metabolic rate depression (MRD) being the most prominent adaptation. MRD is mediated by epigenetic, transcriptional, post-transcriptional, and post-translational mechanisms aimed at shutting down cellular processes that are not needed for anoxia survival, while reprioritizing ATP towards cell processes that are vital for anaerobiosis. Histone acetylation/deacetylation are epigenetic modifications that maintain a proper balance between permissive chromatin and restricted chromatin, yet very little is known about protein regulation and enzymatic activity of the writers and erasers of acetylation during natural anoxia tolerance. As such, this study explored the interplay between transcriptional activators, histone acetyltransferases (HATs), and transcriptional repressors, sirtuins (SIRTs), along with three prominent acetyl-lysine (K) moieties of histone H3 in the liver of red-eared sliders. Western immunoblotting was used to measure acetylation levels of H3-K14, H3-K18, and H3-K56, as well as protein levels of histone H3-total, HATs, and nuclear SIRTs in the liver in response to 5 h and 20 h anoxia. Global and nuclear enzymatic activity of HATs and enzymatic activity of nuclear SIRTs were also measured. Overall, a strong suppression of HATs-mediated H3 acetylation and SIRT-mediated deacetylation was evident in the liver of red-eared sliders that could play an important role in ATP conservation as part of the overall reduction in metabolic rate.
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This work was supported by a Discovery Grant (#6793) awarded to Dr. Kenneth B Storey from the Natural Sciences and Engineering Research Council of Canada (NSERC) and Dr. Kenneth B. Storey holds the Canada Research Chair in Molecular Physiology. Dr. Sanoji Wijenayake holds a NSERC Postdoctoral Research Fellowship at the University of Toronto.
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SW: Conceived and designed the experiment, prepared all material, conducted all experiments, data collection, and analysis and wrote the paper. KBS: Provided all reagents and equipment necessary for the project, provided supervision, and assisted with manuscript writing. All authors read and approved the final manuscript.
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Wijenayake, S., Storey, K.B. Dynamic regulation of histone H3 lysine (K) acetylation and deacetylation during prolonged oxygen deprivation in a champion anaerobe. Mol Cell Biochem 474, 229–241 (2020). https://doi.org/10.1007/s11010-020-03848-x
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DOI: https://doi.org/10.1007/s11010-020-03848-x