Figure 6

Significant overlap between dysregulated genes and GO categories in CK-p25 and TIP60-deficient mice. (A) Rank-rank hypergeometric overlap analysis was used between genes dysregulated in Tip60 cKO and those in CK-p25 mice induced for 2 weeks (ref.³⁶; GSE65159). Each pixel represents a comparison for one gene color-coded for significance (max –log₁₀(p-value) = 2035). The most downregulated genes are at the bottom left corner and the most upregulated ones at the upper right corner of the heatmap. (B) Venn diagrams representing significantly overlapping down- and upregulated genes in Tip60 cKO and CK-p25 mice (2 weeks induction) (ref.³⁶; GSE65159). In each case, the overall significance of the overlaps was determined by permutation tests in which 1000 permutations were performed yielding a highly significant permutation p-value of < 0.0001. (C) H4K12 acetylation levels in Tip60 cKOs and controls at genes downregulated (left) and upregulated (right) in CK-p25 mice. Genes downregulated in CK-p25 mice have significantly decreased H4K12ac levels around their TSS (+ / −2000 bp) in the Tip60 cKO, whereas the upregulated ones do not. Moreover, downregulated genes have higher basal levels of H4K12ac compared to upregulated ones. (D) Quantification of the profile plots in (C). Genes downregulated in 2-week induced CK-p25 mice (ref.³⁶; GSE65159) have significantly decreased H4K12ac levels around their TSS (+ / −2000 bp) in Tip60 cKO, 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 CK-p25): p < 0.0001; Direction effect (downregulated vs upregulated): p < 0.0001; Interaction: p = 0.0085. Post-hoc multiple comparisons for H4K12ac levels (Sidak’s multiple comparison test): downregulated genes: adjusted p-value < 0.0001 (****); upregulated genes: adjusted p-value = 0.3955.