Fig. 5
Broad H3K9ac defines a category of photoreceptor genes vulnerable to downregulation in SCA7. A Heatmap integrating the genome-wide profiles of H3K9ac, H3K27ac and RNAPII densities in WT retina. The window corresponds to the center of H3K9ac peaks ± 5 kb. Heatmaps were obtained from seqMINER with 10 clusters corresponding to different epigenomic states. B, C Graph representing the expression level (B) and RNAPII pausing index (C) of protein coding genes annotated to each cluster in WT retina. n, number of protein coding genes per cluster. Data presented as mean ± SEM and are analyzed using one-way ANOVA followed by Tukey post-hoc test (expression level: F(9, 12072) = 16.37, p < 0.0001; pausing index, F(9, 14075) = 99.63, p < 0.0001). D, E Graphs representing the enrichment of photoreceptor specific (PR) (D) and housekeeping (HK) (E) genes annotated to each cluster. The analysis concerns the distribution of 95 PR genes and 3485 HK genes across all clusters, and bars refer to the ratio of observed versus expected number of genes in each cluster normalized to 1 (dashed red line). The enrichments are 11 × more PR specific genes (pcluster10 = 5.1 × 10–23, hypergeometric test) and 1.6 × less HK genes (pcluster10 = 4.9 × 10–6) than expected in cluster 10. F Gene ontology (GO) analysis of cluster 10. Visual perception and other photoreceptor related processes (bold) are the most significantly enriched biological processes (adj. p value < 0.01) associated with protein coding genes in cluster 10. G Graph comparing the broadness [in base pairs (bp)] of H3K9ac peaks in each cluster in WT and SCA7 retinas. Comparison WT versus SCA7 of cluster 10 using Mann–Whitney test, p < 0.0001. H–J Graph representing the enrichment per cluster of SCA7 upregulated genes (H), 371 SCA7 downregulated photoreceptor identity genes (I) and 536 other downregulated genes (J). The analysis concerns the distribution of each gene category across all clusters, and bars refer to the ratio of observed versus expected number in each cluster normalized to 1 (dashed red line). The enrichments are 7.1 × more photoreceptor identity genes (I) than expected in cluster 10 (pcluster10 = 5.6 × 10–33, hypergeometric test)