Exploring the Epigenetic Fingerprint of Sedentary Behavior

Aim:
Exercise was reported as a stimulator of epigenetic modifications of the chromatin in muscle nuclei (myonuclei); however, it is unclear whether muscle inactivation affects the epigenetic landscape of somatic musculature. We developed an experimental animal-model imitating sedentary behavior in which chromatin epigenetic landscape could be explored.

Methods:
Third-instar Drosophila larvae carrying a temperature-sensitive mutation in shibire gene, coding for GTPase involved in neuronal synaptic vesicle transport, were used. Shibire homozygous mutant larvae are paralyzed at restrictive temperature (>~29°C) due to inhibition of neuromuscular junction vesicular transport; muscle contraction is abolished without affecting other systems. Shibire and control (y,w) larvae were held at 18°C, or 30°C without food for six hours. Larvae were dissected, fixed and double-labeled with antibodies specific for active and repressive epigenetic marks H3K9ac and H3K27me3, respectively.

Results:
At the restrictive temperature (30°C), shibire mutant larvae were paralyzed in contrast to control (shibire at 18°C). In myonuclei of sedentary shibire larvae the repressive mark H3K27me3 decreased significantly relative to similar larvae grown in non-restrictive temperature (p<0.001), and the active/repressed ratio of epigenetic marks (H3K9ac/H3K27me) increased (p<0.001). Epigenetic activation (H3K9ac) did not differ between sedentary and mobile shibire larvae. In contrast, in the control (y,w) the active/repressed (H3K9ac/ H3K27me) ratio decreased (p<0.001).

Conclusion:
In this study, modelling sedentary behavior in youth, muscle inactivity changed the epigenetic fingerprint in myonuclei, with a balance shift towards decreased chromatin methylation relative to acetylation, suggesting decline in the epigenetic control of gene transcription, and reminiscent of decreased epigenetic repression described with aging.