Prolonged fasting increases DNA methylation transiently in Northern elephant seals

Northern elephant seals experience prolonged food and water deprivation (fasting) while breeding, molting, and undergoing postnatal development. Fasting elephant seals adjust neuroendocrine function and gene expression to cope with potentially detrimental effects associated with extended fasting. DNA methylation alters gene expression by modulating accessibility to regions necessary to initiate transcription. We evaluated whether prolonged fasting alters global DNA methylation levels in elephant seal blood. We found that fasting transiently increases DNA methylation in elephant seal pups and that blood DNA methylation correlates with plasma cortisol. Hence, we conducted bioinformatic analyses to identify regions in the elephant seal glucocorticoid receptor (GR) promoter that influence gene transcription through methylation (CPG islands). We identified one CpG island within the putative promoter region of the elephant seal GR gene. Methylation in this region, however, was unaffected by prolonged fasting. We then investigated whether exogenous glucocorticoid treatment alters DNA methylation and gene expression profiles in elephant seal muscle cells in primary culture (myotubes). Exposure to glucocorticoids for 12 or 48 hours decreased DNA methylation while upregulating pro-survival gene expression in seal myotubes. Our results show that whereas prolonged increases in DNA methylation transiently in elephant seal blood, sustained exposure to glucocorticoids decreases DNA methylation and activates a pro-survival transcriptional program in seal myotubes. Therefore, our results suggest that DNA methylation is a plastic, cell-type-specific response that regulates gene expression in fasting elephant seals. Research funded by UC Berkeley This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.