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 energy-enriched diet with longer daylight to simulate summer. As epigenetic marker for active chromatin we quantified genome-wide histone-3 lysine-4 trimethylation (H3K4me3) from liver samples by chromatin immunoprecipitation and high-throughput 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.
Highlights
IntroductionAdaptation to environmental change requires metabolic responses that maintain homeostasis
Adaptation to environmental change requires metabolic responses that maintain homeostasis. Such responses are generated by fast regulation of gene expression through transcription factor binding, and by slow modulation of chromatin structure through epigenetic marks
Our genome-wide scan of differences in H3K4me3 marks induced by mild environmental fluctuations in wild-caught house mice demonstrates the adaptability of epigenetic regulation under near-natural conditions
Summary
Adaptation to environmental change requires metabolic responses that maintain homeostasis. Studies on cell lines or inbred model organisms have uncovered how various epigenetic settings contribute to cellular activity, and an epigenetic code that determines chromatin accessibility has been proposed [1,2] This code comprises DNA methylation states, histone modifications, and non-coding RNA molecules, which together subdivide the genome into active, poised, and silent regions [3,4,5]. Adaptive epigenetic responses can be induced by nutrition, temperature, population density, and stress [6]. These factors have a cumulative effect throughout the life-time of an organism. Historical starvation periods in humans have lead to paternally inherited greater cardiovascular mortality and diabetes risk through epigenetic changes at the imprinted locus INS-IGF2H19 [14,15,16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
