Histone Arginine Methylation in the Freeze-tolerant Wood Frog, Rana sylvatica

The wood frog, Rana sylvatica, is well known for its freeze tolerance ability. To endure winter, frozen frogs switch to a hypometabolic state via transcriptional regulation. Histone methylation is known to play a crucial role in regulating gene transcription. However, histone arginine methylation or demethylation has not previously been studied in the context of freeze tolerance. This thesis presents the first characterization of arginine methylation in a freeze tolerant vertebrate. Overall, levels of protein arginine methyltransferases (PRMTs) and methylated histone residues showed differential regulation over the freeze/thaw-cycle in wood frog liver. All PRMTs and downstream targets showed no changes during freezing, but protein levels of targets associated with transcription activation were elevated during thaw in skeletal muscle. Differential levels of histone demethylases were found in both tissues among the experimental conditions. These results indicate a role for histone methylation in supporting metabolic rate depression and tissue homeostasis during freezing.