This data includes regulatory factor profiling using DNase and ChIP-seq and methylation profiling using bisulfite-seq. Overall design: We investigated CTCF occupancy in the context of reduced methylation by performing genome-wide profiling with chromatin immunoprecipitation (ChIP-seq) in HCT116 cells and DNMT1 and DNMT3B double knockout (DKO) HCT116 cells. We also profiled HCT116 and DKO using DNaseI-seq and ChIP-seq for trimethylation of histone 3 lysine 4 (H3K4me3) and acetylation of histone 3 lysine 27 (H3K27ac), Finally, we performed ChIP-seq on 3 replicates of mock-treated and 2 replicates of 5-aza-CdR-treated K562 cells.