Aberrant hypermethylation colocalizes to CpG islands and CG clusters. (A) The genomic position of every HpaII-amplifiable fragment on the HELP array was compared with the location of known CpG islands and CG clusters, and the fragments on the array were divided into 2 categories: those overlapping with either one of these genomic elements and those not overlapping. To determine whether the differentially methylated genes between CEBPA^sil and CEBPA^mut leukemias were enriched for either one of these types of elements, a proportions test was used to compare the relative proportion of the 2 types of HpaII fragments in the signature (overlapping vs not overlapping) to the relative proportion on the array. Stacking bars are used to illustrate the finding of a significant enrichment for HpaII-amplifiable fragments overlapping with CpG islands (right) and CG clusters (left) in the hypermethylated signature of CEBPA^sil leukemia, as it compares with the genomic localization of all HpaII-amplifiable fragments on the HELP array. (B) Each HpaII-amplifiable fragment represented on the HELP array was also categorized according to its ability to discriminate between CEBPA^sil and CEBPA^mut leukemias as perfect, intermediate, or poor classifiers, and the proportional amount of fragments overlapping with CG clusters was calculated for each group of classifiers. Better classifiers were more frequently associated with CG clusters.