Red-eared sliders (Trachemys scripta elegans) are champion anaerobes that can survive approximately three months of absolute anoxia at 3 °C and recover with minimal cellular injury. Although various physiological and biochemical adaptations are involved in anoxia tolerance, metabolic rate depression (MRD) is considered to be the most useful response. T.s. elegans can reduce their metabolic rate to 10% of normoxic values by reducing all energy expensive cellular processes including gene expression. However, adaptations of alternate transcriptional regulatory processes are mostly unknown. In the thesis, epigenetic regulation of anoxia tolerance was investigated by exploring the dynamic changes in DNA methylation/demethylation, histone acetylation/deacetylation, and histone lysine methylation during short-term (5 h) anoxia and long-term (20 h) anoxia in several tissues of red-eared sliders. DNA methylation significantly increased in the liver and white skeletal muscle. An increase in DNA methylation could indicate a potential decrease in global gene expression in response to oxygen deprivation in red-eared sliders. Correspondingly, a genomic mark of active transcription, DNA demethylation, decreased in the liver and white skeletal muscle. Establishing a unique balance between global and localized DNA methylation could be an important component of anoxia tolerance. Histone lysine methylation was also anoxia responsive in the liver of red-eared sliders, and suggested a target-specific regulation that could potentially aid in the selective upregulation of genes that are necessary for anoxia survival, while suppressing others. Histone acetylation and deacetylation, implicated in MRD of other stress-tolerant animals, illustrated a strong suppression in the liver of red-eared sliders. A strong suppression in histone H3 acetylation may also indicate an overall decrease in gene expression. Overall, this thesis may enhance our understanding of alternate modes of transcriptional regulation during anoxia tolerance and report several epigenetic mechanisms that are involved the hypometabolic response in T.s. elegans.