MM cells display widespread alterations in enhancer activity. (A) Overlap between active H3K27Ac-marked enhancers in MM (11 primary MM and 10 MM cell lines) and the ENCODE and Roadmap Epigenome enhancer catalogs. Total number of H3K27Ac-marked regions is indicated in parentheses for each group. (B) Number of elements showing similar or differential (twofold) H3K27Ac signals when comparing primary MM (n = 11), PB (n = 3), and memB (n = 3). (C) Box and whisker plots of the fold change in RNA expression (comparing MM and PBs) for genes with or without DEs with gained or lost H3K27Ac signal. (D) MM-related genes displaying increased expression and H3K27Ac signals in primary MM (black tracks) compared with PBs (red tracks) and memB (green tracks). Arrows indicate enhancers. Expression (average FPKM ± standard deviation) of the gene in each loci is shown below the tracks. (E) GREAT analysis of enhancers with gained activity in MM compared with PBs. Top 6 significant Molecular Signatures Database (MSigDB) Perturbation terms are shown. X-axis displays enrichment P values (−log₁₀). (F) De novo identification of TF motifs enriched in enhancers with gained H3K27Ac signal in MM compared with PBs (gained DEs). The best TF motif matches, P values for motif enrichment, and percentage of regions containing motif are indicated to the right of the sequence logos. (G) Distribution of enriched motifs in the gained DEs. BPC, bone marrow plasma cell; HP, hyperploid; MF, MAF/MAFB; TPC, tonsil plasma cell.