RRBS Profiling of Clonal Cell Lines with Different Circadian Period

Composed of negative feedback loops, circadian oscillations are thought to be noise-resistant. Yet, individual cells in culture are remarkably heterogenous, oscillating independently and with different period lengths. To assess whether differential methylation contributes to heritable heterogeneity of circadian periods, we used reduced representation bisulfite sequencing (RRBS) to explore DNA methylation profiles and their correlation with the transcriptome in the 10 clonal cell lines. To investigate the mechanisms underlying this heterogeneity, we generated and characterized hundreds of clonal cell lines from the same parent culture. By comparing clonal lines with different circadian periods, we identified a group of differentially methylated regions (DMRs). Overall design: Divided 10 clonal cell lines into 2 groups based on circadian period length. Compare DNA methylation profiles from different groups to identify differentially methylated regions (DMRs) potentially responsible for circadian periodicity determination.