Item

Abstract

Wild house mice form social hierarchies with aggressive males defending territories, in
which females, young mice and submissive adult males share nests. In contrast, socially
excluded males are barred from breeding groups, have numerous bite wounds and patches
of thinning fur. Since their feeding times are often disrupted, we investigated whether social
exclusion leads to changes in epigenetic marks of metabolic genes in liver tissue.We used
chromatin immunoprecipitation and quantitative PCR to measure enrichment of two activating
histone marks at 15 candidate loci. The epigenetic profiles of healthy males sampled
from nest boxes differed significantly from the profiles of ostracized males caught outside of
nests and showing bite wounds indicative of social exclusion. Enrichment of histone-3
lysine-4 trimethylation (H3K4me3) changed significantly at genes Cyp4a14, Gapdh, Nr3c1,
Pck1, Ppara, and Sqle. Changes at histone-3 lysine-27 acetylation (H3K27ac) marks were
detected at genes Fasn, Nr3c1, and Plin5. A principal components analysis separated the
socialized from the ostracized mice. This was independent of body weight for the H3K4me3
mark, and partially dependent for H3K27ac. There was no separation, however, between
healthy males that had been sampled from two different nests. A hierarchical cluster analysis
also separated the two phenotypes, which was independent of body weight for both
markers. Our study shows that a period of social exclusion during adult life leads to quantitative
changes in histone modification patterns in mouse liver tissue. Similar epigenetic
changes might occur during the development of stress-induced metabolic disorders in
humans.