We compare histone modifications, chromatin accessibility, and replication timing domain genome-wide in HCT116 colon cancer cells with its genetic derivative DKO cells which lack DNMT3B and DNMT1 activity and the fibrosarcoma cell line HT1080. Overall design: This submission contains the following experiments on HCT116, DKO (DNMT1-/-;DNMT3b-/-), and HT1080 cells: 3 biological replicates of Protect-seq for each cell lines using Illumina and 1 Oxford Nanopore run on HCT116, 1 replicate of WGS on DKO and HT1080 for Protect-seq input, 2 biological replicates of H3K9me2, H3K9me3, H3K27me3, HP1alpha, CTCF, and input ChIP-seq and Early and Late fractions of Repli-seq for HT1080 cells. 1 biological replicate of H3K9me2, H3K9me3, HP1beta, HP1alpha, H3, and input ChIP-seq for HCT116 and DKO cells.