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. Author manuscript; available in PMC: 2019 Feb 9.
Published in final edited form as: Cancer Cell. 2018 Mar 12;33(3):435–449.e6. doi: 10.1016/j.ccell.2018.02.006

Figure 1: NRL and CRX are master regulators of the photoreceptor program in Group 3 MB.

Figure 1:

(A, B) Results of GO/Pathway analysis showing gene sets associated with either Group 3 gene expression signatures (A) or Group 3-specific enhancer-gene targets (B) (from Lin et al., 2016). Nodes represent enriched pathways and are sized according to significance; edge weight corresponds to the degree of shared genes between nodes. (C) TF interaction network showing the top fully interconnected network of SE-associated TFs as ranked by highest aggregate clique score for TFs within the network. (D) Schematic representation of NRL and CRX gene regulation and their respective binding motifs. (E, F) Left, Meta tracks of H3K27ac ChIP-seq signal (reads per million per base pair, rpm/bp) across MB subgroups at the NRL (E) and CRX (F) loci. Bottom, meta tracks of OTX2 ChIP-seq signals in the D425MED Group 3 MB cell line (Hovestadt et al., 2014). Right, Bar plots of NRL (E) and CRX (F) expression in corresponding samples. Error bars represent ± SEM. (G) Bar plots showing NRL and CRX mRNA levels (FPKM) across primary Group 3 MB samples included in the study (n=8). Dashed line represents the threshold used to identify NRL and CRX high expression samples. Yellow/gray shading designates the NRL/CRX high vs. low samples, respectively. (H) Waterfall plot showing Group 3 active genes (x-axis) ranked by the average log2 fold change in enhancer and promoter H3K27ac load (y-axis) between NRL/CRX high vs. low tumors (n=4 each). (I) Leading edge enrichment plots for the top gene sets (from MSigDB C2 curated) enriched in NRL/CRX low (left, negatively correlated) or NRL/CRX high (right, positively correlated) expression Group 3 samples as defined in (H). (J, K) Meta tracks of H3K27ac ChIP-seq signal (rpm/bp) for NRL/CRX high vs. low expression Group 3 MBs at the CACNA2D1 (J) and ERN1 (K) loci. (L) Bar plots showing CACNA2D1 (right) and ERN1(left) mRNA levels (FPKM) across NRL/CRX high vs. low expression samples. See also Figure S1 to S4 and Table S1 and S2.