Dynamic regulation of histone H3 lysine (K) acetylation and deacetylation during prolonged oxygen deprivation in a champ
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Dynamic regulation of histone H3 lysine (K) acetylation and deacetylation during prolonged oxygen deprivation in a champion anaerobe Sanoji Wijenayake1,2 · Kenneth B. Storey1,3 Received: 15 April 2020 / Accepted: 20 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Epigenetics · Anoxia · T.s. elegans · Histone lysine acetyltransferases · Sirtuins · Histone H3
Introduction Freshwater turtles belonging to the Chrysemys and Trachemys genre are champion anaerobes that can survive approximately 90 days of continual anoxia at 3 °C and recover with minimal cellular injury [1–4]. Red-eared sliders (Trachemys scripta elegans) employ numerous well-adapted strategies * Kenneth B. Storey [email protected] 1
Department of Biology, Institute of Biochemistry, Carleton University, Ottawa, ON, Canada
2
Present Address: Department of Biological Sciences and Center for Environmental Epigenetics and Development, University of Toronto, Toronto, ON, Canada
3
Canada Research Chair in Molecular Physiology, Department of Biology, and Department of Chemistry, Institute of Biochemistry, 1125 Colonel By Drive, Ottawa, ON K1S 5B6, Canada
to combat challenges that are associated with anaerobiosis, including (1) increase glycogen storage in liver, white skeletal muscle, and heart, (2) exclusively use anaerobic gl
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