Figure 2.
HDAC1 is recruited at BRD4 dense enhancers in CLL. (A) BRD4 and H3K27Ac tag intensity and signal was used to quantitate the association of BRD4 at enhancers (SEs and TEs) and shows that 382 (CLL251228), 312 (CLL2501776), and 245 (CLL250275) genes were loaded with BRD4-dense marks at SEs. HDAC tag intensity and signal determine was used to determine the association of HDAC1 at BRD-linked enhancers and shows that HDAC was strongly recruited at 335 (88%) (CLL251228), 284 (91%) (CLL2501776), and 215 (88%) (CLL250275) (in red) of the BRD4-dense SEs. Similarly, HDAC1 was corecruited at 3423 (71% - CLL250228), 4096 (51% - CLL250776), and 4110 (42% - CLL 250275) (in blue) out of a total of 4775 (CLL251228), 7970 (CLL251776), and 9772 (CLL251275) genes that had BRD4 associated with TEs. (B) ROSE analysis was performed using the BRD4 load and intensity at H3K27Ac-marked enhancers. The plots represent the top BRD4 loaded enhancers that also recruited dense HDAC loads in 3 representative CLL samples. HDAC1-bound, BRD4-dense SEs (marked in red) are listed in decreasing order of enhancer rank. Selected genes bound by HDACs with BRD4 at TEs are marked in blue. SE and TE identification for all samples are listed in supplemental Table 4. (C) TOPPGene Suite was used to derive functional annotations of the top biological processes associated with HDAC1 bound at BRD-SEs. Top 25 pathways (based on z-scores) associated with the genes are shown and color coded based on specificity from orange to blue, whereas the size reflects the number of genes that make up the category. (D) Overlay of HDAC1, BRD4, H3K9Ac, H3K27Ac, ATAC-seq profiles, and RNA Pol II densities at selected top genes from CLL251228 showing HDAC1 loads at BRD4 dense SEs in cluster I (i-vi) CXCR4, IL4R, BCL2, IKZF3, PAX5, and BLK from CLL251228. Each track is representative of the ChIP-seq binding densities for specified genes from 3 independent samples from patients with CLL (CLL251228, CLL251776, and CLL251275). The x-axis of each track shows genomic position, and the y-axis shows the intensity of the ChIP signal (rpm/bp). ROSE, rank ordering of super-enhancers.

HDAC1 is recruited at BRD4 dense enhancers in CLL. (A) BRD4 and H3K27Ac tag intensity and signal was used to quantitate the association of BRD4 at enhancers (SEs and TEs) and shows that 382 (CLL251228), 312 (CLL2501776), and 245 (CLL250275) genes were loaded with BRD4-dense marks at SEs. HDAC tag intensity and signal determine was used to determine the association of HDAC1 at BRD-linked enhancers and shows that HDAC was strongly recruited at 335 (88%) (CLL251228), 284 (91%) (CLL2501776), and 215 (88%) (CLL250275) (in red) of the BRD4-dense SEs. Similarly, HDAC1 was corecruited at 3423 (71% - CLL250228), 4096 (51% - CLL250776), and 4110 (42% - CLL 250275) (in blue) out of a total of 4775 (CLL251228), 7970 (CLL251776), and 9772 (CLL251275) genes that had BRD4 associated with TEs. (B) ROSE analysis was performed using the BRD4 load and intensity at H3K27Ac-marked enhancers. The plots represent the top BRD4 loaded enhancers that also recruited dense HDAC loads in 3 representative CLL samples. HDAC1-bound, BRD4-dense SEs (marked in red) are listed in decreasing order of enhancer rank. Selected genes bound by HDACs with BRD4 at TEs are marked in blue. SE and TE identification for all samples are listed in supplemental Table 4. (C) TOPPGene Suite was used to derive functional annotations of the top biological processes associated with HDAC1 bound at BRD-SEs. Top 25 pathways (based on z-scores) associated with the genes are shown and color coded based on specificity from orange to blue, whereas the size reflects the number of genes that make up the category. (D) Overlay of HDAC1, BRD4, H3K9Ac, H3K27Ac, ATAC-seq profiles, and RNA Pol II densities at selected top genes from CLL251228 showing HDAC1 loads at BRD4 dense SEs in cluster I (i-vi) CXCR4, IL4R, BCL2, IKZF3, PAX5, and BLK from CLL251228. Each track is representative of the ChIP-seq binding densities for specified genes from 3 independent samples from patients with CLL (CLL251228, CLL251776, and CLL251275). The x-axis of each track shows genomic position, and the y-axis shows the intensity of the ChIP signal (rpm/bp). ROSE, rank ordering of super-enhancers.

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