Environmental circadian disruption alters rhythmicity of clock and epigenetic gene expression in SKH-1 female mouse livers

Endogenous circadian rhythms are primarily entrained by environmental cues that are used to regulate the function of cells and peripheral tissues throughout the body. We found that disrupted light schedules – reflective of shift work conditions – demonstrated impaired gene expression throughout the 24-h day in core clock and epigenetically regulated genes. Dysregulated expression in these genes has been independently detected in the etiology of sleep-related diseases, suggesting epigenetic regulation as a potential mechanistic link between circadian disruption and health outcomes. Because of this, we hypothesized that epigenetic regulatory factors are circadian expressed and can be dysregulated by environmental circadian disruption. In this study, we show rhythmic expression of both core clock and epigenetic genes in female SKH-1 mouse livers under normal circadian conditions and the subsequent effect of disrupted clocks thereafter. To address our hypothesis, we measured relative gene expression patterns in female mouse livers under healthy and disrupted clock conditions. In 5 of the 8 core clock genes (Cry1, Cry2, Npas2, Nr1d1, Per2), there was a significant loss of rhythmic expression. All active demethylases and Zfp57 experienced a loss of rhythmicity due to clock disruption, while both de novo DNMTs, Dnmt3a and Dnmt3b, displayed a slight damping of rhythmicity in disrupted clock mice.