Several conclusions can be made from this catalogue of CG-DMRs. First, reprogramming a somatic cell to a pluripotent state generates hundreds of aberrantly methylated loci, predominantly at CG islands and associated with genes. Second, whereas insufficient reprogramming manifested as a memory of the progenitor somatic cell methylation state is common, a high incidence of iDMRs unlike both the progenitor somatic cell and ES cells indicates that aberrant methylation patterns dissimilar to both the start and endpoints of the reprogramming process are frequently generated. Third, although there is variability in the loci that are differentially methylated between iPSC lines, a high proportion of CG-DMRs are found in multiple independent iPSC lines, indicating that these regions have a strong propensity to be insufficiently or aberrantly reprogrammed. Fourth, a core set of CG-DMRs was present in every iPSC line, representing hotspots of failed epigenomic reprogramming common to iPSCs. Fifth, both memory CG-DMRs and iDMRs are transmitted through differentiation of the iPSCs at a high frequency, indicating that the disrupted DNA methylation states are not simply a transient aberration during the pluripotent state. The
