Extended Data Fig. 8: ZIC1 regulates Gli2 and cell cycle pathway genes in granule cells.

a, Number of ChIP–seq peaks identified from Flag-tagged ZIC1 ChIP–seq in granule neuron progenitor (GNP) cells transduced with wild-type (WT) ZIC1 or group 4 (G4) medulloblastoma ZIC1 mutant. Two biological replicates were generated for WT ZIC1 and three for G4 medulloblastoma ZIC1 mutants. b, Distribution of normalized reads for WT vs. G4 medulloblastoma mutant Flag-tagged ZIC1-transduced GNP cells across peaks identified from FLAG ChIP–seq. c, Schematic summarizing the RNA-seq libraries generated from mouse granule lineage cells. d, Top 10 pathways downregulated by ZIC1 overexpression compared to empty vector in bulk granule cells and GNPs. e, Expression level of GLI2 across different medulloblastoma molecular subgroups. Plot was generated using the RNA-seq cohort used in the study (N = 311). GLI2 exhibits a highly SHH medulloblastoma-specific expression pattern. Center of box—median. Bounds of box—25% and 75% percentile. Whiskers show minimum and maximum values within the 1.5× interquartile range. P values calculated by two-tailed Mann–Whitney U test. f, Zic1/2 ChIP–seq track demonstrating presence of peaks on the Gli2 promoter in 2 immunoprecipitation replicates but not in input (data for f–h from GSE60731). g, Volcano plot summarizing genes differentially expressed by knocking down Zic1 from mouse GNP. P adjusted threshold = 0.05. h, Normalized counts of Gli2 transcript in control shRNA and Zic1 shRNA treated GNP. Biological sample size = 2 for each arm. P adjusted value was obtained from DESeq2 differential expression analysis.