Extended Data Fig. 5: The effect of seRNA m6A on H3K4me3 modification in PDAC cells. | Nature Genetics

Extended Data Fig. 5: The effect of seRNA m6A on H3K4me3 modification in PDAC cells.

From: Super-enhancer RNA m6A promotes local chromatin accessibility and oncogene transcription in pancreatic ductal adenocarcinoma

Extended Data Fig. 5

a, The RPKM values of H3K4me3 (left), H3K27ac (middle) and H3K4me1 (right) ChIP-seq within the center of seRNA-associated chromatin and its 2 kilobases flanking regions categorized into top-50% or bottom-50% based on the m6A levels. b, Density of the distance between H3K4me3 modification determined by ChIP-seq and the seRNA m6A site. Data from GSE31755. c, Reduced H3K4me3 modification probability (curve) and level (box plot, n = 3,217) in hypo-m6A seRNA related chromatin in CFL1 KO cells. d, The averaged H3K4me3 signals in seRNA without m6A site related chromatin in CFL1 KO and KO-control cells (n = 12,092). The y axis represents log2 of read counts. e, The genomic distribution of upregulated (Up) or downregulated (Down) H3K4me3 peaks in CFL1 KO cells. f, Overlap between CFL1 KO unchanged H3K4me3 regions and CFL1 KO hypo-m6A-seRNAs. g, Boxplots showing the differential H3K4me3 levels (CFL1 KO vs non-KO) within super-enhancers with different number of RRACH motifs (high: n = 2,128; low: n = 2,128). h, Density of the H3K4me3 CUT&Tag-seq signals as function of m6A peak intensity. m6A peaks were categorized into low (n = 1,410), medium (n = 1,418), and high groups (n = 1,428). P value by Kruskal-Wallis’s test. i, The portions of downregulated, upregulated and unchanged seRNAs in CFL1 KO versus KO-control cells. j, The overlap between CFL1 KO downregulated seRNAs and CFL1 KO hypo-m6A seRNAs (left), and CFL1 KO downregulated H3K4me3 regions (middle) or CFL1 CLIP peaks in seRNAs (right). k, Percentage of differentially expressed CFL1-related m6A seRNAs in 65 PDAC samples (left) and CFL1 KO cells (right). l, Boxplots showing the differential H3K4me3 levels (CFL1 KO versus non-KO) within the indicated subgroups, sample size: CFL1 KO: n = 2. KO-Control: n = 2. m, Snapshots of UCSC genome browser showing m6A levels and H3K4me3 levels in two seRNAs and their associated chromatin regions. Grey, input; blue, IP in non-KO; red, IP in CFL1 KO; orange, H3K4me3 CUT&Tag. IgG as negative control. P in (c), (d), (g) and (l) values by two-sided Wilcoxon rank-sum tests.

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