English: The results from a previous publication (McGarvey et al., 2008) are summarized here to reflect what has been learned, through performance of Agilent 244K whole genome ChiP-chip analyses of key histone modifications for verified and candidate genes with promoter, CpG island, DNA hypermethylation in the HCT 116 line of human colon cancer cells. The top panel shows, for these cells, average results for the 7.0 kB proximal promoter regions for > 4,500 active genes with non-DNA methylated, CpG island–containing promoters. Note the enrichment of the active H3K4me2 mark on either side of the transcription start sites and the very low levels of the PcG mediated H3K27me3 mark. The middle panels shows the average results for the marks in the same regions of over 40 verified genes with full silencing, and heavily DNA methylated, CpG island promoters (Schuebel et al., 2007; McGarvey et al., 2008). The exact pattern was found for over 6oo such candidate DNA hypermethylated genes in the HCT 116 cells revealed by an expression array discovery approach (Schuebel et al., 2007; McGarvey et al., 2008). Note the marked reduction in levels of, and different positioning of, the active H3K4me2 mark, and a low but distinct level of the H3K27me3 mark broadly distributed over the proximal promoter regions. In the bottom panel, the analysis of the same genes shown in the middle panel have benn performed in an isogenic line of HCT 116 cells, DKO, in which two DNMT’s, DNMT1 and 3b, have been genetically deleted. This maneuver effectively eliminates most of the overall DNA methylation in the cells including in the promoters of the genes analyzed (Rhee et al., 2002). Note the persistence, and even some increase in the H3K27me3 mark. Simultaneously, there is enrichment and re-positioning of the H3K4me2 mark towards the status seen in the active genes in the top panel. This simultaneous pattern for the two marks in the DKO cells, as circled and labeled, resembles bivalent chromatin as per the text.