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Abstract:
In mammals, exposure to toxic or disease-causing environments can change epigenetic marks that are inherited
independently of the intrauterine environment. Such inheritance of molecular phenotypes may be adaptive. However,
studies demonstrating molecular evidence for epigenetic inheritance have so far relied on extreme treatments, and are
confined to inbred animals. We therefore investigated whether epigenomic changes could be detected after a non-drastic
change in the environment of an outbred organism. We kept two populations of wild-caught house mice (Mus musculus
domesticus) for several generations in semi-natural enclosures on either standard diet and light cycle, or on an energyenriched
diet with longer daylight to simulate summer. As epigenetic marker for active chromatin we quantified genomewide
histone-3 lysine-4 trimethylation (H3K4me3) from liver samples by chromatin immunoprecipitation and highthroughput
sequencing as well as by quantitative polymerase chain reaction. The treatment caused a significant increase of
H3K4me3 at metabolic genes such as lipid and cholesterol regulators, monooxygenases, and a bile acid transporter. In
addition, genes involved in immune processes, cell cycle, and transcription and translation processes were also differently
marked. When we transferred young mice of both populations to cages and bred them under standard conditions, most of
the H3K4me3 differences were lost. The few loci with stable H3K4me3 changes did not cluster in metabolic functional
categories. This is, to our knowledge, the first quantitative study of an epigenetic marker in an outbred mammalian
organism. We demonstrate genome-wide epigenetic plasticity in response to a realistic environmental stimulus. In contrast
to disease models, the bulk of the epigenomic changes we observed were not heritable.
