Fig. 3: H3K27 acetylation and accessibility dynamics after NFKB2 knock down reveal putative p52-dependent enhancers.

a Loci displaying differential H3K27 acetylation and accessibility as well as p52 binding signal in KMS-11 cells. b Downregulated or upregulated H3K27 acetylation and accessibility signals, centred on p52 binding sites throughout the genome, in KMS-11 control (ctrl) versus p52 KD cells. Scatter plot showing correlation between H3K27 acetylation and accessibility dynamics at p52 binding sites following p52 disruption. c H3K27 acetylation and MM accessibility signal dynamics across p52-dependent H3K27ac peaks identified in KMS-11. d Matched RNA-seq and e MMRF expression dynamics of nearest 5 genes to p52-dependent H3K27ac peaks found to have enriched accessibility or H3K27 acetylation in NF-κB+ MM samples. 3 groups of peak/gene pairs are defined: Depleted (n = 1747), Enriched (n = 2452) and Other (n = 213192). Lower and upper hinges correspond to first and third quartiles. Central value corresponds to the median. Whiskers extend to largest/smallest values no further than 1.5 x IQR (Interquartile range). Pairwise-comparison p-values determined by 2-sided Wilcoxon rank sum tests and adjusted for multiple comparisons (Benjamini-Hochberg). f Somatic CYLD frameshift insertion putatively detected in multiple myeloma sample MM17 from RNA-seq data. g Somatic TRAF3 frameshift insertion putatively detected in multiple myeloma samples MM15 and MM29 from RNA-seq data. Similar somatic mutations recorded in other cancers are shown based on TCGA data. Such mutations are implicated to contribute to constitutive activation of the ncNF-κB pathway.