Chromosomal locations of DMRs in pre- versus postdecitabine treatment AML samples. The 4 lanes above each chromosome symbol show the number of DMRs in 400-kb bins as a heat map for all genomic features (ALL), CpG islands (CGI), Gene deserts (GD), and RefSeq gene bodies (RG), respectively (intensity in each lane is normalized to the bin with most DMRs in that lane). These 4 features were selected as they depict genomic features with diverse CpG densities (see Table 1 for other features evaluated in this study but not shown here). Comparing the 4 heat map tracks shown here (ALL vs CGI, or GD, or RG), the most significant number of DMRs induced by decitabine treatment is contributed by the CpG islands. This effect of decitabine is most pronounced at the chromosome ends (exception: chromosome 3, chromosome 15, and chromosome Y). The green track below the chromosome symbol shows the distribution of CpG islands (CGIs) across the chromosome (independently of their methylation status). Because CpG islands are also enriched in chromosome ends, we performed Pearson χ2 analysis of observed DMRs versus expected DMRs for every 400-kb bin in the genome (“Chromosomal localization of DMRs”) to test whether enrichment of DMRs within the chromosome ends is related to the higher density of CpG islands in that region or as a nonrandom effect of decitabine treatment. The resulting P values are plotted in the χ2 track in blue. For all chromosomes except 2, 3, 15, 19, and 21, the P values were significant (P ≤ .05) at least at one end of the chromosome, indicating significant clustering of DMRs not accounted for by the dense distribution of CpG islands in that region of the chromosome.
