Figure 3.

Acetylation and rearrangement of BCL6 locus enhancers. A. H3K27ac ChIP-Seq tracks across the BCL6 locus in 29 B cell populations. Green bars at bottom indicate the median positions of detected super-enhancer regions. Black brackets indicate published breakpoint cluster regions. Read-pairs spanning the tandem duplication in HGB-04 are linked by red bars at bottom. The legend at left indicates the super-enhancers called in each population, as well as populations classified as HGB (red = ABC-DLBCL, green = GCB-DLBCL, blue = PMBL, black = HGB cell line). MEF2B-positive (black arrows) and selected MEF2B-negative TF binding sites (open arrows) are indicated, and correspond to positions indicated in (C). ChIP-seq coverage range is 0-5 fpm (fragments per million mapped fragments) for all tracks. B. Normalized RNA expression of BCL6 in HGB biopsies. Samples are numbered and color-coded by subtype as in Figure 2C. Solid boxes indicate samples evaluated by PEAR-ChIP. Symbols indicate samples that contain a genomic lesion proximal to the measured gene (plus sign: enhancer tandem duplication, pound sign: FISH-detected rearrangement between the MYC and BCL6 loci). C. ChIP-Seq tracks for p300, H3K27ac, and three TFs in two HGB cell lines at the BCL6 promoter and super-enhancer regions. MEF2B-positive (black arrows) and selected MEF2B-negative TF binding sites (open arrows) are indicated and correspond to positions indicated in (A). ChIP-Seq coverage range is 0-15 fpm for H3K27ac. D. Relative BCL6 expression in MCL and HGB cell lines stably transduced with pINDUCER-20 bearing a GFP or MEF2B-HA transgene, and harvested 48 hours after induction with 100 ng/ml doxycycline. E. ChIP-seq tracks for H3K27ac and HA-tag in Jeko-1 cells with induced expression of GFP or MEF2B-HA as in figure 4b. Genomic positions and arrows are identical to (C). ChIP-seq coverage range is 0-2.5 fpm for H3K27ac.