Figure 5
From: TIP60/KAT5 is required for neuronal viability in hippocampal CA1
Reduction of H4K12ac binding mostly affects the promoter regions of downregulated genes in Tip60 cKO mice. (A) Principal component analysis of the ChIP-Seq data shows a pronounced separation between the genotypes. (B) Heatmap of the promoter regions with significantly changed H4K12ac binding (adjusted p-value < 0.05 and |fold change| > 1.2). (C) GO category analysis for genes with decreased H4K12ac at their promoters (same genes as in (B)). (D,E) Average levels of H4K12ac at the promoters (D) and gene bodies (E) of every gene that is downregulated in the RNA-Seq analysis (adjusted p-value < 0.05 and |fold change| > 2). (F) H4K12 acetylation (H4K12ac) levels along the genes downregulated (left) and upregulated (right) in Tip60 cKO mice. (G) Genes downregulated in Tip60 cKO mice have significantly decreased H4K12ac levels around their TSS (+ / −2000 bp), whereas the upregulated ones do not. Moreover, downregulated genes have higher basal levels of H4K12ac compared to upregulated ones. Two-Way ANOVA: Genotype effect (control vs Tip60 cKO): p < 0.0001; Direction effect (downregulated vs upregulated): p < 0.0001; Interaction: p = 0.0041. Post-hoc multiple comparisons for H4K12ac levels (Sidak’s multiple comparison test): downregulated genes: adjusted p-value < 0.0001 (****); upregulated genes: adjusted p-value = 0.5431. (H) H4K12ac levels along learning-related genes downregulated (left) and DNA replication-related genes (right) upregulated in Tip60 cKO mice. (I) Learning-related genes downregulated in Tip60 cKO mice have significantly decreased H4K12ac levels around their TSS (+ / −2000 bp), whereas DNA replication-related genes upregulated in Tip60 cKO mice do not. Moreover, those learning-related genes have higher basal levels of H4K12ac compared to the ones related to DNA replication. Two-Way ANOVA: Genotype effect (control vs Tip60 cKO): p < 0.0001; Type effect (Learning-Related vs DNA Replication-Related): p < 0.0001; Interaction: p = 0.0018. Post-hoc multiple comparisons for H4K12ac levels (Sidak’s multiple comparison test): Learning-Related Genes: adjusted p-value < 0.0001 (****); DNA Replication-Related Genes: adjusted p-value = 0.3293.
