Liver transcriptomic and methylomic analyses identify transcriptional mitogen-activated protein kinase regulation in facultative hibernation of Syrian hamster

Author:

Coussement Louis1ORCID,Oosterhof Marloes M.23,Guryev Victor4,Reitsema Vera A.2,Bruintjes Jojanneke J.2,Goris Maaike2,Bouma Hjalmar R.25,de Meyer Tim1,Rots Marianne G.3,Henning Robert H.2

Affiliation:

1. Department of Data Analysis and Mathematical Modelling, Faculty of Bioscience Engineering, Ghent University, B-9000 Ghent, Belgium

2. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands

3. Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands

4. European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands

5. Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands

Abstract

Hibernation consists of alternating torpor–arousal phases, during which animals cope with repetitive hypothermia and ischaemia-reperfusion. Due to limited transcriptomic and methylomic information for facultative hibernators, we here conducted RNA and whole-genome bisulfide sequencing in liver of hibernating Syrian hamster ( Mesocricetus auratus ). Gene ontology analysis was performed on 844 differentially expressed genes and confirmed the shift in metabolic fuel utilization, inhibition of RNA transcription and cell cycle regulation as found in seasonal hibernators. Additionally, we showed a so far unreported suppression of mitogen-activated protein kinase (MAPK) and protein phosphatase 1 pathways during torpor. Notably, hibernating hamsters showed upregulation of MAPK inhibitors (dual-specificity phosphatases and sproutys) and reduced levels of MAPK-induced transcription factors (TFs). Promoter methylation was found to modulate the expression of genes targeted by these TFs. In conclusion, we document gene regulation between hibernation phases, which may aid the identification of pathways and targets to prevent organ damage in transplantation or ischaemia-reperfusion.

Funder

Talent PhD scholarship to MO by the Graduate School of Medical Sciences, University of Groningen

Stichting De Cock-Hadders

Publisher

The Royal Society

Subject

General Agricultural and Biological Sciences,General Environmental Science,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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