Immunoelectron microscopic characterization of nucleolus‐associated domains during hibernation

Malatesta, Manuela; Zancanaro, Carlo; Biggiogera, Marco

doi:10.1002/jemt.20872

Cited by 8 publications

(7 citation statements)

References 47 publications

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“…et al, 2007) considering that altered nucleolus structure and aggregation of RNA binding proteins into subnuclear particles has been reported during hibernation (Malatesta et al, 2011;.…”

Section: Discussionmentioning

confidence: 99%

Dynamic changes in global and gene specific DNA methylation during hibernation in adult thirteen-lined ground squirrels,Ictidomys tridecemlineatus

Alvarado

Mak

Liu

et al. 2015

Journal of Experimental Biology

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Hibernating mammals conserve energy in the winter by undergoing prolonged bouts of torpor, interspersed with brief arousals back to euthermia. These bouts are accompanied by a suite of reversible physiological and biochemical changes; however, much remains to be discovered about the molecular mechanisms involved. Given the seasonal nature of hibernation, it stands to reason that underlying plastic epigenetic mechanisms should exist. One such form of epigenomic regulation involves the reversible modification of cytosine bases in DNA by methylation. DNA methylation is well known to be a mechanism that confers upon DNA its cellular identity during differentiation in response to innate developmental cues. However, it has recently been hypothesized that DNA methylation also acts as a mechanism for adapting genome function to changing external environmental and experiential signals over different time scales, including during adulthood. Here, we tested the hypothesis that DNA methylation is altered during hibernation in adult wild animals. This study evaluated global changes in DNA methylation in response to hibernation in the liver and skeletal muscle of thirteen-lined ground squirrels along with changes in expression of DNA methyltransferases (DNMT1/3B) and methyl binding domain proteins (MBDs). A reduction in global DNA methylation occurred in muscle during torpor phases whereas significant changes in DNMTs and MBDs were seen in both tissues. We also report dynamic changes in DNA methylation in the promoter of the myocyte enhancer factor 2C (mef2c) gene, a candidate regulator of metabolism in skeletal muscle. Taken together, these data show that genomic DNA methylation is dynamic across torporarousal bouts during winter hibernation, consistent with a role for this regulatory mechanism in contributing to the hibernation phenotype.

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“…et al, 2007) considering that altered nucleolus structure and aggregation of RNA binding proteins into subnuclear particles has been reported during hibernation (Malatesta et al, 2011;.…”

Section: Discussionmentioning

confidence: 99%

Dynamic changes in global and gene specific DNA methylation during hibernation in adult thirteen-lined ground squirrels,Ictidomys tridecemlineatus

Alvarado

Mak

Liu

et al. 2015

Journal of Experimental Biology

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“…They suggested that storage at the cleavage stage could allow for immediate renewal of translation which fits with the need for the rapid activation of brown adipose metabolism to support thermogenesis that must begin instantly when arousal starts. Immunocytochemistry also revealed changes in the molecular composition of the nucleolus during hibernation (Malatesta et al, 2011). Ultrastructure analysis showed the appearance of nucleolus-associated domains during hibernation …”

Section: Reviewmentioning

confidence: 94%

Regulation of hypometabolism: insights into epigenetic controls

Storey

2015

Journal of Experimental Biology

146

129

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For many animals, survival of severe environmental stress (e.g. to extremes of heat or cold, drought, oxygen limitation, food deprivation) is aided by entry into a hypometabolic state. Strong depression of metabolic rate, often to only 1-20% of normal resting rate, is a core survival strategy of multiple forms of hypometabolism across the animal kingdom, including hibernation, anaerobiosis, aestivation and freeze tolerance. Global biochemical controls are needed to suppress and reprioritize energy use; one such well-studied control is reversible protein phosphorylation. Recently, we turned our attention to the idea that mechanisms previously associated mainly with epigenetic regulation can also contribute to reversible suppression of gene expression in hypometabolic states. Indeed, situations as diverse as mammalian hibernation and turtle anoxia tolerance show coordinated changes in histone post-translational modifications (acetylation, phosphorylation) and activities of histone deacetylases, consistent with their use as mechanisms for suppressing gene expression during hypometabolism. Other potential mechanisms of gene silencing in hypometabolic states include altered expression of miRNAs that can provide post-transcriptional suppression of mRNA translation and the formation of ribonuclear protein bodies in the nucleus and cytoplasm to allow storage of mRNA transcripts until animals rouse themselves again. Furthermore, mechanisms first identified in epigenetic regulation (e.g. protein acetylation) are now proving to apply to many central metabolic enzymes (e.g. lactate dehydrogenase), suggesting a new layer of regulatory control that can contribute to coordinating the depression of metabolic rate.

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“…When other nuclear bodies like Cajal bodies were found embedded into the nucleolus, their morphology was still recognizable. 11,12 Moreover, these foci are different also from the nucleolus-associated domains described by Malatesta et al 13 in tissues from hibernating mammals.…”

Section: Discussionmentioning

confidence: 70%

Discrete foci containing RNAse A are found in nucleoli of HeLa cells after aging in culture

et al. 2011

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We have studied by means of ultrastructural immunocytochemistry the localization of RNase A in nuclei of HeLa cells in control conditions and following cell ageing in culture. We have found that roundish, electron dense foci, which contain a significant amount of RNase A, can be detected within nucleoli of aged cells. These bodies also contain RNA and lack ribosomal S3 proteins, and may represent either simple storage sites or areas where RNA degradation takes place.

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Immunoelectron microscopic characterization of nucleolus‐associated domains during hibernation

Cited by 8 publications

References 47 publications

Dynamic changes in global and gene specific DNA methylation during hibernation in adult thirteen-lined ground squirrels,Ictidomys tridecemlineatus

Dynamic changes in global and gene specific DNA methylation during hibernation in adult thirteen-lined ground squirrels,Ictidomys tridecemlineatus

Regulation of hypometabolism: insights into epigenetic controls

Discrete foci containing RNAse A are found in nucleoli of HeLa cells after aging in culture

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