Ectopic MAF is sufficient to convert chromatin from an inert to an activatory state. (A) Volcano plot of transcriptome after MAF overexpression in the U266 myeloma cell line compared with empty vector (EV) control. MAF itself as well as indicative known MAF target genes are highlighted. (B) Metagene accessibility profiles seen in MAF-overexpressing U266 cells compared with EV control cells, genome-wide (overall, blue) and in MAF-associated regions (red). (C) M versus A plot of differential accessibility after MAF overexpression, focusing on the MAF-associated regions. Highlighted are the MAF-activated promoters and MAF-activated enhancers, in red and orange, respectively. Pie charts depicting a fraction of MAF-associated regions with increased or reduced accessibility in MAF-overexpressing cells and percentage of MAF-activated promoters and enhancers in each. (D) Ratios of open vs closed differential accessibility regions after MAF overexpression, with P-value representing hypergeometric distribution test (E) Fraction of MAF-activated promoters and enhancers showing enhanced accessibility in MAF-overexpressing U266 cells. (F) Heatmap depicting fold change in signal or corresponding gene expression for each of the opened MAF-activated promoters and enhancers after MAF overexpression. (From left to right) MAF ChIP-seq; fold change over input in ChIP-seq of MAF in MM.1S, MAF vs ND ATAC-seq; log2fold change in the ATAC-seq signal of primary MAF MM samples when compared with healthy PCs, MAF vs EV ATAC-seq; log2fold change in ATAC-seq signal in MAF-overexpressing U266 cells when compared with EV control, Beta (ChIP-seq + knockdown (kd) RNA-seq); beta score of change in gene expression after MAF shRNA-mediated knockdown in MM.1S cells, MAF vs ND RNA-seq; log2fold change in gene expression in primary MAF MM samples when compared with healthy PCs; MAF vs EV RNA-seq; and log2fold change of gene expression in MAF-overexpressing U266 cells when compared with EV control.