Genome Wide Transcript and Methylation Changes in the Sheep Seasonal Clock

The circannual clock drives yearly rhythms, in both plants and animals, to meet the challenges of a changing seasonal environment. For many agricultural species the seasonal timing of growth, metabolism and reproduction is synchronized to the changing length of day (photoperiod). We investigated epigenetic and transcriptional changes in sheep calendar cells of the pituitary pars tuberalis (PT).

We present a genome-wide analysis of the changes in DNA methylation with respect to melatonin treatment, photoperiod, and time of day (circadian effect). We correlated methylation changes to proximal gene expression. RRBS and RNASeq was used to measure methylation and transcript abundance. Beta-regression analysis was used to dissect the effects and interaction of effects from a melatonin implant, photoperiod and time of day on methylation.

We observed significant methylation changes in response to melatonin treatment (426 FDR significant CpG sites), photoperiod lengthening (1,697), and time of day (567). We identified 529 significant DMR regions. Photoperiod had the strongest effect on the methylome. Melatonin was shown to effect methylation changes and play a role as an important interactor that modulates the methylation effects of photoperiod and time of day. We also observed differences and overlaps in the location and density of methylation changes across the genome for all three treatments. Correlation between methylation and transcript abundance was dependent on the overlap with genomic features.

We conclude that the epigenome of PT calendar cells plays an important role in the circannual clock. It drives seasonal changes in the transcriptome, orchestrating the timing of seasonal processes.