Mammalian hibernation: differential gene expression and novel application of epigenetic controls

Abstract

This review highlights current information about the regulatory mechanisms that govern gene expression during mammalian hibernation, in particular the potential role of epigenetic controls in coordinating the global suppression of transcription. Hibernation is characterized by long periods of deep torpor (when core body temperature drops to near ambient) that are interspersed with brief arousal periods back to euthermia. Entry into torpor requires coordinated controls which strongly suppress and reprioritize all metabolic functions, including global controls on both transcription and translation. At the same time, however, selected hibernation-specific genes are up-regulated under the control of specific transcription factors to support the torpid state; this includes genes that encode proteins involved in lipid fuel catabolism and in long term cytoprotection (e.g. antioxidants, chaperones). We evaluate the currently available information on global transcriptional suppression in hibernation and propose that epigenetic mechanisms such as DNA methylation, histone modification, SUMOylation and the actions of sirtuins play crucial roles in transcriptional suppression during torpor. Global controls providing translational suppression also occur during hibernation including reversible phosphorylation control of ribosomal initiation and elongation factors as well as polysome dissociation. We also present initial data that mRNA transcripts are regulated via inhibitory interactions with microRNA species during torpor and provide the first evidence of differential expression of miRNAs in hibernators. When taken together, these mechanisms provide hibernators with multiple layers of regulatory controls that achieve both global repression of gene expression and selected enhancement of genes/proteins that achieve the hibernation phenotype.

Epigenetics and transgenerational transfer: a physiological perspective

“…Indeed, the study of mammals that are able to alternate between two extremely different physiological states (i.e. hibernation) has shed some light on a wide array of potential epigenetic controls of metabolic rate suppression (Morin and Storey, 2009). Also consider, for example, that biologists generally assume that any paternal contribution to epigenetic effects is strictly through the germ line, because in many animals little other than the sperm and some modest amounts of supporting fluids are transferred at mating.…”

Aestivation: signaling and hypometabolism

“…Histone modifications include acetylation and phosphorylation, which reduce chromatin packing to increase transcription factor accessibility to gene promoters, and methylation, which acts oppositely. In hibernating mammals, relative levels of histone acetylation and phosphorylation decrease during torpor and activities of histone deacetylases rise, all indicative of transcriptional silencing (Morin and Storey, 2009). Only one study to date has approached epigenetic regulation in aestivation.…”

Ion channels/transporters as epigenetic regulators? —a microRNA perspective

“…Another group has also illustrated that the expression of multiple miRNAs was significantly altered following the exposure of human articular chondrocytes to hyperosmotic conditions [31]. Apart from these, a study investigating the possible role of miRNAs in the regulation of mammalian hibernation found that miR-1 and miR-21 were both significantly increased in the kidneys of hibernating versus euthermic animals, providing the first evidence of differential expression of miRNAs in response to temperature control in mammals [32]. Taken together, these studies support the notion that miRNA regulation in response to microenvironmental changes may contribute to cellular physiology and abnormality of such regulation may be involved in pathological processes.…”