Figure 2.

Loss of DNA methylation results in the reorganization of nucleosomes and the acquisition of active and poised chromatin marks at CGI promoters. (A) Average NOMe-seq methylation levels (CG methylation for “DNA Methylation” and GC methylation for “Accessibility”) were aligned to transcription start sites (TSSs) of 15,638 CGI promoters and extended by ±1 kb. The heatmap was organized into four sections based on the DNA methylation levels: Unmethylated in HCT116 and Unmethylated in DKO1 (UU); Methylated in HCT116 and Methylated in DKO1 (MM); and Methylated in HCT116 and Unmethylated in DKO1 (MU). Within each class, promoters were ordered based on hierarchical clustering of the accessibility pattern in DKO1 cells (a similar clustering based on the accessibility of HCT116 cells is shown in Supplemental Fig. 2A). (B) In each cell type, Pearson correlations were calculated based on methylation levels between pairs of GCs at each possible distance from one another. Only those pairs in which both GCs were from 0 to 700 bp downstream from the TSS were considered. (C) Within each promoter class, the Z-score enrichment level of each histone mark was extended to ±3 kb around the TSS and averaged (see Methods for Z-score enrichment definition). (D) FPKM transcript values for all genes were divided into three levels, and the fraction within each level is shown along with error bars indicating the standard error across two RNA-seq biological replicates.