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Multi‐Tissue Chromatin Modulation During Hibernation
Author(s) -
Dhillon Rashpal S,
Krautkramer Kimberly A,
Denu John M,
Carey Hannah V
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.889.3
Subject(s) - torpor , histone , chromatin , biology , acetylation , microbiology and biotechnology , nucleosome , histone methylation , histone code , dna methylation , biochemistry , dna , endocrinology , thermoregulation , gene , gene expression
Hibernation is characterized by a dramatic reduction in energy demand that profoundly alters metabolic state. Changes in metabolic rate during torpor‐arousal cycles affect levels of circulating metabolites, which in turn have the potential to induce dynamic alterations in histone acetylation and methylation status. Eukaryotic histone‐modifying enzymes are known to be sensitive to levels of small molecule metabolites. The fundamental unit of chromatin is the nucleosome, which is comprised of a core of histone proteins that is wrapped ~2.5 times by genomic DNA. Histones are small, globular proteins with highly flexible N‐terminal tails that are subject to a multitude of covalent post‐translational modifications which dictate how accessible genomic DNA is to processes such as transcription and replication. In this study, we investigate how different metabolic and nutritional phases across the annual hibernation cycle affects histone modifications in multiple tissues of thirteen‐lined ground squirrels. Liver, brain, and brown adipose tissue were analyzed in squirrels sampled in summer, winter torpor, winter interbout arousal (IBA) and spring phases. Using an in‐house LC‐MS/MS workflow, we identified > 50 distinct chromatin signatures that segregate by tissues and metabolic/nutritional state. Hierarchical clustering shows that histone post translational modification (PTM) states of brain and brown adipose are more similar to one another than either are to liver. Histone acetylation, which has a significantly shorter half‐life than histone methylation, generally associates with more rapid switches in metabolic state (i.e., torpor vs. IBA). In contrast, switches between torpor and either of the two fed states (spring, summer) associate with changes in histone methylation. Collectively, our results suggest that the robust metabolic and nutritional shifts associated with hibernation drive changes in chromatin state.