Fig. 7: CREBBP and KMT2D haploinsufficiency cooperatively impairs activation of super-enhancers controlling GC B cell fate decisions. | Nature Communications

Fig. 7: CREBBP and KMT2D haploinsufficiency cooperatively impairs activation of super-enhancers controlling GC B cell fate decisions.

From: Loss of CREBBP and KMT2D cooperate to accelerate lymphomagenesis and shape the lymphoma immune microenvironment

Fig. 7

a, c, d Left: box plots showing C/K/CK deficiency-induced changes in chromatin accessibility in mouse GC B cells (a, enhancers: n = 33,448, super-enhancers: n = 3746), or H3K27ac in OCI-Ly7 cells (c, enhancers: n = 2737, super-enhancers: n = 616) at enhancer and constituent super-enhancer peaks, or changes in the target gene expression of CK-co-bound promoters, enhancers, and super-enhancers in OCI-Ly7 cells (d, n = 5411, 1959, 2031 genes respectively). The middle line in the box marks median. The box vertical size denotes IQR. The upper and lower hinges correspond to 25th and 75th percentiles. The upper and lower whiskers extend to the maximum and minimum values that are within 1.5 × IQR from the hinges. Right: bar plots showing the mean log2FC of chromatin accessibility (a), H3K27ac (c), or RNA (d), with error bars indicating 95% confidence intervals (C.I.) of the mean. b Waterfall plot ranking super-enhancers (SE) in mouse GC B cells based on their accessibility change in CK vs WT. Constituent ATAC-seq peaks in each SE were summed before calculating the fold change. Genes linked to red-highlighted closing SEs were downregulated in CK vs WT. e Waterfall plots ranking super-enhancers in OCI-Ly7 cells based on their H3K27ac changes in C (left), K (middle) or CK (right) vs WT. Constituent H3K27ac peaks in each SE were summed before calculating the fold change. Bar colors represent NES values of RNA-seq GSEA, using all genes in each SE-residing TAD as gene signature against ranked gene list based on their expression changes in C/K/CK vs WT. Highlighted genes were downregulated and linked to the corresponding SEs. Red line indicates log2FC cut off of −0.58. f IGV views of normalized histone marks CUT&RUN and RNA-seq signals at the indicated loci in isogenic OCI-Ly7 cells. H3K27ac Hi-ChIP loop calls are depicted as arcs connecting the two interacting loci. Promoters and super-enhancers are shaded in gray and yellow colors, respectively.

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