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Fig. 2 | Acta Neuropathologica Communications

Fig. 2

From: C11orf95-RELA fusion drives aberrant gene expression through the unique epigenetic regulation for ependymoma formation

Fig. 2

Most RELAFUS1 target genes are actively transcribed. a Genome-wide RELAFUS1-HA binding or H3K27ac marks in mEPN (H1203) cells. The enrichment of H3K27ac within the RELAFUS1-HA binding region is shown in heatmaps. b Bar graphs display the genomic distribution of the RELAFUS1 peaks in H1203 cells. c, e Volcano plots illustrating differences in gene expression between RCAS-RELAFUS1-driven ependymomas (FUS1) and mouse normal brains (NB) (c) or RCAS-PDGFA-driven glioblastomas (PDGFA) (e) (FDR < 0.05, n = 11,574 (c), n = 8,059 (e)). Differences in Log2 fold change in gene expression values are plotted on the x-axis. Adjusted p values calculated using the Benjamin-Hochberg method are plotted on the y-axis. RELAFUS1 target genes annotated within the TSS ± 10 kb in H1203 cells are shown as large circles. 2700081O15Rik, Ccnd1 and Lmx1b genes are indicated by the arrows. d, f Scatter plots showing the mRNA expression of direct RELAFUS1 target genes in the DEGs (logFC) between RELAFUS1-driven ependymomas and normal brains (d) or PDGFA-driven glioblastomas (f). Genes are grouped based on the distance of the RELAFUS1 binding to location to the TSS of the gene (FDR < 0.05, ± 50 kb- ± 1 kb; n = 1,083, 943, 826, 668, 511, 412, 342 and 295). The expression level of DEGs bound by RELAFUS1 within the TSS ± 10 kb were compared to those bound by RELAFUS1 at other distances as indicated in the x-axis. g, h Venn diagram showing the number of the overlapping of up- and down-regulated RELAFUS1 target genes (within TSS ± 10 kb) in RELAFUS1-driven ependymomas relative to normal brains or PDGFA-driven glioblastomas. i Venn diagram showing the number of the overlapping of H3K27ac peaks in H41 plus H1203 cells and RELAFUS1 peaks in H1203 cells. j Venn diagram showing the number of the overlapping of RELAFUS1 peaks and super-enhancers (SEs) identified in H1203 cells. k Inflection plots representing SEs in H41 and H1203 cells. Representative genes are shown along with their rankings. l, m Venn diagrams showing the number of the overlapping of Rela peaks in MEFs after 3 h of TNF stimulation (see Methods) and RELAFUS1 peaks in H1203 cells (l) or H3K27ac peaks within the entire genome (m) in H41 and H1203 cells. n, o Venn diagrams showing the number of the overlapping of Rela target genes in MEFs and RELAFUS1 target genes in H1203 (n) or 293T (o) cells. Statistical tests are as described in Fig. 1

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