Evaluating the Stability and Flexibility of DNA Methylation Patterns from Stem to Differentiated Cells

DNA methylation has been studied extensively in many developmental systems. Little attention, however, has been given to identifying methylation features that distinguish loci whose patterns are in flux in a given cell lineage from those whose patterns are stable. Here, we develop a new metric, the Ratio of Concordance Preference (RCP), to quantify and compare epigenetic flexibility and stability across loci, cell types, and developmental stages, without assuming any specific biochemical mechanisms. We apply RCP to double-stranded DNA methylation data from human and murine cells and conclude that: (i) preference for concordant DNA methylation is reduced but not eliminated in stem relative to differentiated cells; (ii) cellular differentiation is characterized by increasing preference for concordant methylation states; and (iii) while concordance preference remains substantial through embryonic totipotency and early stages of pluripotency, primordial germ cells initially have nearly no preference for concordance, perhaps reflecting the high level of epigenetic flexibility en route to production of gametes. The mechanism-free nature of RCP will enable 1/33 peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/072488 doi: bioRxiv preprint first posted online Aug. 31, 2016;