The genome sequences at the CG-DM Rs present in all iPSC lines were analysed to identify motifs that could be associated with the altered DNA methylation states. Binding sites for two human transcription factors were identified in sequences conserved over the DMRs, corresponding to the reprogramming factor KLF4 and the chromatin-remodelling factor FOXL1 (Supplementary Fig. 11). Given that KLF4 has previously been found to bind to the promoter of FAM19A5 in H1 ES cells at precisely the same genomic position as one of the 11 hypermethylated iDMRs shared between all iPSC lines18, it is tempting to speculate that development of the conserved aberrant methylation states in the iPSC lines may be related to altered expression of the endogenous and/or introduced copy of KLF4 during the reprogramming process.
