Figure 8.

Functional genomics identifies transcriptional activities affected by mHtt. A, Spearman correlation coefficients for TFBS enrichment in each dataset pair are presented as a heatmap. We compared the gene lists corresponding to significantly altered transcripts in HD82Q hippocampus (Hp) and cerebellum (Cb), R6/2 striatum (Str R6/2), caudate nucleus of HD patients (human) and hypo- and hyperacetylated TSS retrieved in our ChIPseq screen in HD82Q hippocampus. A good correlation was observed between the enrichment for TFBSs in the promoter of deacetylated genes (HYPO) and that in downregulated genes (DOWN) for the different HD models. In contrast, the enrichment in hyperacetylated genes (HYPER, only shown for AcH3K9,14 given the rarity of H4K12 hyperacetylation events) did not correlate with that in upregulated genes (UP). B, Heatmap presenting the significance of TFBS enrichment for motifs that were consistently retrieved in the analysis of downregulated genes in the different expression profiles described above. The significance of the enrichment for the same TFBSs in the three gene sets defined in Figure 7A is also shown. The color palette indicates the P value range; white: nonsignificant (P > 0.05).