Dynamic regulation of six histone H3 lysine (K) methyltransferases in response to prolonged anoxia exposure in a freshwater turtle

Wijenayake, Sanoji; Hawkins, Liam J.; Storey, Kenneth B.

doi:10.1016/j.gene.2018.01.086

Cited by 34 publications

(28 citation statements)

References 79 publications

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“…This may be of some interest, as extracellular histones H2A and H4 in crocodile blood have indeed been identified to act as inhibitors of viral (HIV) infection in vitro (94). While some studies in reptiles have assessed histone deacetylation, methylation, and histone variants (158-160), as well as linking histone methylation to anoxia survival in turtles (161), studies on posttranslational deimination of histones is lacking in non-avian reptiles. Histone H3 deimination has been previously identified inked to inflammatory responses during CNS regeneration in the chicken (Gallus gallus) (40) and in hypoxic responses during CNS repair (41).…”

Section: Discussionmentioning

confidence: 99%

Deimination Protein Profiles in Alligator mississippiensis Reveal Plasma and Extracellular Vesicle-Specific Signatures Relating to Immunity, Metabolic Function, and Gene Regulation

et al. 2020

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Alligators are crocodilians and among few species that endured the Cretaceous-Paleogene extinction event. With long life spans, low metabolic rates, unusual immunological characteristics, including strong antibacterial and antiviral ability, and cancer resistance, crocodilians may hold information for molecular pathways underlying such physiological traits. Peptidylarginine deiminases (PADs) are a group of calcium-activated enzymes that cause posttranslational protein deimination/citrullination in a range of target proteins contributing to protein moonlighting functions in health and disease. PADs are phylogenetically conserved and are also a key regulator of extracellular vesicle (EV) release, a critical part of cellular communication. As little is known about PAD-mediated mechanisms in reptile immunology, this study was aimed at profiling EVs and protein deimination in Alligator mississippiensis. Alligator plasma EVs were found to be polydispersed in a 50-400-nm size range. Key immune, metabolic, and gene regulatory proteins were identified to be posttranslationally deiminated in plasma and plasma EVs, with some overlapping hits, while some were unique to either plasma or plasma EVs. In whole plasma, 112 target proteins were identified to be deiminated, while 77 proteins were found as deiminated protein hits in plasma EVs, whereof 31 were specific for EVs only, including proteins specific for gene regulatory functions (e.g., histones). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed KEGG pathways specific to deiminated proteins in whole plasma related to adipocytokine signaling, while KEGG pathways of deiminated proteins specific to EVs included ribosome, biosynthesis of amino acids, and glycolysis/gluconeogenesis pathways as well as core histones. This highlights roles for EV-mediated export of deiminated protein cargo with roles in metabolism and gene regulation, also related to cancer. The identification of posttranslational deimination and EV-mediated communication Criscitiello et al. Deimination and EV Signatures in Alligator in alligator plasma revealed here contributes to current understanding of protein moonlighting functions and EV-mediated communication in these ancient reptiles, providing novel insight into their unusual immune systems and physiological traits. In addition, our findings may shed light on pathways underlying cancer resistance, antibacterial and antiviral resistance, with translatable value to human pathologies.

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Section: Discussionmentioning

confidence: 99%

Deimination Protein Profiles in Alligator mississippiensis Reveal Plasma and Extracellular Vesicle-Specific Signatures Relating to Immunity, Metabolic Function, and Gene Regulation

et al. 2020

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“…For example, one recent study documented epigenetic changes that dynamically occur on histone proteins to alter the chromatin state in a manner that is responsive to anoxia. This suggests chromatin-level regulation of gene expression in an anoxia-responsive manner in the turtle (Wijenayake, Hawkins & Storey, 2018). Given the large amount of supporting knowledge behind the molecular mechanisms that permits this turtle to survive extended periods of anoxia, we chose the red-eared slider turtle as the most appropriate model for this study.…”

Section: Introductionmentioning

confidence: 99%

Navigating oxygen deprivation: liver transcriptomic responses of the red eared slider turtle to environmental anoxia

Biggar

Zhang

Storey

2019

PeerJ

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The best facultative anaerobes among vertebrates are members of the genera Trachemys (pond slider turtles) and Chrysemys (painted turtles), and are able to survive without oxygen for up to 12 to 18 weeks at ∼3 °C. In this study, we utilized RNAseq to profile the transcriptomic changes that take place in response to 20 hrs of anoxia at 5 °C in the liver of the red eared slide turtle (Trachemys scripta elegans). Sequencing reads were obtained from at least 18,169 different genes and represented a minimum 49x coverage of the C. picta bellii exome. A total of 3,105 genes showed statistically significant changes in gene expression between the two animal groups, of which 971 also exhibited a fold change equal to or greater than 50% of control normoxic values. This study also highlights a number of anoxia-responsive molecular pathways that are may be important to navigating anoxia survival. These pathways were enriched in mRNA found to significantly increase in response to anoxia and included molecular processes such as DNA damage repair and metabolic reprogramming. For example, our results indicate that the anoxic turtle may utilize succinate metabolism to yield a molecule of GTP in addition to the two molecules that results from lactate production, and agrees with other established models of anoxia tolerance. Collectively, our analysis provides a snapshot of the molecular landscape of the anoxic turtle and may provide hints into the how this animal is capable of surviving this extreme environmental stress.

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“…The molecular mechanisms that underlie anoxia tolerance adaptations include: post-translational modifications, epigenetic regulation, transcription factor regulation, the accumulation of organic osmolytes, and the post-transcriptional regulation of small regulatory non-coding RNAs called microRNAs (miRNAs) (Szereszewski and Storey, 2018;Wijenayake et al, 2018;Biggar and Storey, 2017;Green and Storey, 2016;Kornfeld et al, 2012;Krivoruchko and Storey, 2010;Muir et al, 2007). miRNAs are highly conserved sequences of non-coding RNA approximately 22 nucleotides long that have been identified as critical regulators of a diverse range of cellular functions through their ability to suppress translation (Lund et al, 2004;Christopher et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs regulate survival in oxygen-deprived environments

English

Hadj‐Moussa

Storey

2018

Journal of Experimental Biology

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Some animals must endure prolonged periods of oxygen deprivation to survive. One such extreme model is the northern crayfish (Orconectes virilis), that regularly survives year-round hypoxic and anoxic stresses in its warm stagnant summer waters and in its cold, ice-locked winter waters. To elucidate the molecular underpinnings of anoxia resistance in this natural model, we surveyed the expression profiles of 76 highly conserved microRNAs in crayfish hepatopancreas and tail muscle from normoxic, acute 2 h anoxia, and chronic 20 h anoxia exposures. MicroRNAs are known to regulate a diverse array of cellular functions required for environmental stress adaptations, and here we explored their role in anoxia tolerance. The tissue-specific anoxia responses observed herein, with 22 anoxia-responsive microRNAs in the hepatopancreas and only four in muscle, suggest that microRNAs facilitate a reprioritization of resources to preserve crucial organ functions. Bioinformatic microRNA target enrichment analysis predicted that the anoxia-downregulated microRNAs in hepatopancreas targeted Hippo signalling, suggesting that cell proliferation and apoptotic signalling are highly regulated in this liverlike organ during anoxia. Compellingly, miR-125-5p, miR-33-5p and miR-190-5p, all known to target the master regulator of oxygen deprivation responses HIF1 (hypoxia inducible factor-1), were anoxia downregulated in the hepatopancreas. The anoxia-increased transcript levels of the oxygen-dependent subunit HIF1α highlight a potential critical role for miRNA-HIF targeting in facilitating a successful anoxia response. Studying the cytoprotective mechanisms in place to protect against the challenges associated with surviving in oxygenpoor environments is critical to elucidating the vast and substantial role of microRNAs in the regulation of metabolism and stress in aquatic invertebrates.

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Dynamic regulation of six histone H3 lysine (K) methyltransferases in response to prolonged anoxia exposure in a freshwater turtle

Cited by 34 publications

References 79 publications

Deimination Protein Profiles in Alligator mississippiensis Reveal Plasma and Extracellular Vesicle-Specific Signatures Relating to Immunity, Metabolic Function, and Gene Regulation

Deimination Protein Profiles in Alligator mississippiensis Reveal Plasma and Extracellular Vesicle-Specific Signatures Relating to Immunity, Metabolic Function, and Gene Regulation

Navigating oxygen deprivation: liver transcriptomic responses of the red eared slider turtle to environmental anoxia

MicroRNAs regulate survival in oxygen-deprived environments

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