Fig. 5: Ablation of SNAI2 enables MYOD to activate myogenic target genes. | Nature Communications

Fig. 5: Ablation of SNAI2 enables MYOD to activate myogenic target genes.

From: Interaction between SNAI2 and MYOD enhances oncogenesis and suppresses differentiation in Fusion Negative Rhabdomyosarcoma

Fig. 5

a Composite plots showing SNAI2 signal intensities (reads per million mapped reads) at SNAI2 high confidence peaks (n = 1069) in SMS-CTR (top) and RD (bottom). b Heatmaps of SNAI2 peak intensity at SNAI2 high confidence peaks. Each row represents a genomic ___location and is centered around SNAI2 peaks, extended 4 kb in each direction, and sorted by SNAI2 signal strength. c Composite plots showing MYOD signal intensities at SNAI2 high confidence peaks (left) and at MYOD peaks (right) in SMS-CTR and RD. RPMPR, Reads Per Million Mapped Peak Reads. d Bubble plot depicting Gene Set Enrichment Analysis (GSEA) in SMS-CTR and RD cells (left). The size of the bubble is proportional to the −log10 nominal (NOM) p, and the color of the bubble corresponds to the normalized enrichment score (NES) value. GSEA enrichment plots showing positive enrichment for a set of genes up-regulated during differentiation of human skeletal muscle myoblasts into myotubes (right, top), and a set of myogenically induced super-enhancer genes (right, bottom). p values are determined by the GSEA algorithm relative to the null distribution calculated with 1000 permutations. For each of the enrichment plots shown here, the false discovery rate (FDR) q value and the nominal p value is <0.0005. e Diagram illustrating SNAI2 direct or indirect myogenic target genes through EDEN analysis. SE, Super Enhancer; TAD, Topologically Associated Domain. f Sites of direct SNAI2 mediated gene suppression at MYOG, MYBPH (left), and MEF2A (right), with both H3K27ac HiChIP for 3D chromatin folding and ChIP-seq. Representative ChIP-seq tracks are shown for MYOD, SNAI2, H3K27ac, and delta (Δ) value (shSNAI2.1 minus shScr) in MYOD and SNAI2 and gene expression (RNA-seq) at MYOG, MYBPH, and MEF2A loci in SMS-CTR. Arrows depict SNAI2/MYOD regulation on direct target myogenic genes. RPMPR, Reads Per Million Mapped Peak Reads; RRPM, Reference-adjusted Reads Per Million Mapped Reads; RPM, Reads Per Million Mapped Reads.

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