Fig. 6

Summary of methylation responses at known and putative imprinted gDMR. a Changes in methylation seen in 3abKO cells rescued with DNMT3A2 for all of the known and putative gDMRs. Eleven gDMRs of fourteen which could be assayed showed gains in methylation, with nine of these reaching significance. KvDMR, Grb10 and 6330408a02Rik failed to recover methylation levels, instead showing significant additional reductions in methylation when compared to the 3abKO ES cells. b Absolute methylation levels in the 3abKO + 3a2 cells at the various gDMR. c Schematic summarising the changes in methylation seen in the two types of knockout and rescue. WT ESC cells grown in petri dishes were derived originally from inner cell mass (ICM) of early embryo and retained 50% methylation at most imprinted gDMR (half-filled bars: paternal at left, maternal at right). While loss of DNMT1 (pathway 1, top) gave comparable hypomethylation to loss of DNMT3A/B (pathway 2, bottom), no recovery of methylation at either paternally or maternally methylated imprinted gDMRs was seen in DNMT1-rescued cells, whereas rescue with DNMT3A2 in 3abKO cells restored methylation non-discriminately at both paternally and maternally imprinted gDMRs (pathway 2)