Tighe Bloskie, M.Sc. Biology 2021

Methyl epigenetic mechanisms in the freeze-tolerance response of Rana sylvatica nervous tissue


Wood frog freeze tolerance is a classic example of metabolic rate depression (MRD), which facilitates reprioritization of minimal anaerobic resources to pro-survival pathways. Global gene expression is consequentially suppressed due, in part, to transcriptional controls, but to date, specific mechanisms have received little attention. Methylation of DNA and histone lysine residues are common epigenetic mechanisms that are tightly associated with control of transcription and thus have been implicated in MRD. However, preliminary findings appeared tissue- and species-specific, and considering research into nervous tissues was lacking, further investigation is required. This thesis tracks the expression and activity of some key methyl epigenetic modifiers like lysine/DNA methyltransferases and DNA demethylases, as well as selected putative targets across the wood frog freeze-thaw cycle and associated sub-stresses. This thesis provides strong evidence in favour of roles for H3K9 and DNA hypomethylation during freeze recovery, which are largely correlated with changes in expression of catalyzing enzymes. Some non-histone target roles are also suggested. Alleviation of repressive epigenetic controls likely contribute to the resumption of a permissive transcriptional state and may induce the activity of essential repair pathways during thawing.