Fig. 6

Aberrant E2F regulation coincides with increased p53 signaling and cell-cycle gene expression in HD astrocytes. Cross-sectional GSEA enrichment plots shows significant depletion of E2F target gene expression in HD NPCs (a) and significant enrichment in HD astrocytes (b) compared to WT cells. Black lines indicate E2F target gene positions in rank-sorted expression data between HD and WT samples. Red dots indicate leading edge genes. q values are FDR corrected p values with alpha = 0.02, or the equivalent. RNA-seq expression data for E2F1 (c) and E2F7 (d) showing differential expression corresponding with motif accessibility. Average FPKM for each sample was plotted. Error bars show 95% confidence intervals (**p < 0.001 and *p < 0.01, differential expression analysis). e Heatmap depicting nearest differential ATAC-seq peaks to E2F target genes that are DE in at least one stage of astrocyte differentiation. Both proximal and distal peaks are included. Nearest differential ATAC-seq peaks are arranged according to hierarchical clustering, and correspond to the gene order in panel F. The E2F1 motif is shown below the heatmap. f Heatmap depicting differential expression of E2F target genes across differentiation. Each row corresponds to the same gene and gene names are displayed to the right of the plot. For both heat maps, red represents HD enrichment and blue indicates HD depletion. g Track view of RNA-seq and ATAC-seq data, as well as motifs present in differential peaks, at MCM3, an example E2F target gene. HD signal is shown in red and WT in blue. Significant differential peaks are indicated in the tracks below ATAC-seq tracks at each stage. TF motifs enriched in differential peaks are displayed at the bottom