Supplementary Figure 6: HDAC3 and MeCP2 regulate the recruitment of FOXO transcription factors to gene promoters.
From: Histone deacetylase 3 associates with MeCP2 to regulate FOXO and social behavior
(a) UCSC genome browser view at the Arrdc2 locus of HDAC3 ChIP-seq coverage in the hippocampus of P45 wild-type and Mecp2 KO mice. (b) Aggregate plots of average HDAC3 ChIP-seq signal in P45 wild-type hippocampus (blue) and Mecp2 KO hippocampus (purple). Aggregate plots were generated at the TSS of genes upregulated in the hippocampus of Mecp2 KO mice27. HDAC3 ChIP-seq signal at the TSS of genes with the lowest expression in P45 hippocampus27 (black; negative control; 10% of total genes). TSS, transcriptional start site. (c) Aggregate plots of average HDAC3 ChIP-seq signal in P45 wild-type hippocampus (blue) and Mecp2 KO hippocampus (purple). Aggregate plots were generated at the TSS of genes downregulated in the hippocampus of Mecp2 KO mice. HDAC3 ChIP-seq signal at the TSS of genes with the lowest expression in P45 hippocampus27 (black; negative control; 10% of total genes). TSS, transcriptional start site. (d) ChIP of MeCP2 and IgG followed by qPCR at the promoters of Arrdc2, Dusp4, Klf10, Tle1, Bdnf and Nr4a1 in hippocampus of wildt-ype and Mecp2 KO mice (% input). One-way ANOVA; Arrdc2, F(2,9) = 12.62, ** P = 0.0024; Dusp4, F(2,9) = 28.96, **** P < 0.0001; Klf10, F(2,9) = 14.84, ** P = 0.0014; Tle1, F(2,9) = 14.39, ** P = 0.0016; Bdnf, F(2,9) = 8.119, ** P = 0.0097; Nr4a1, F(2,9) = 5.996, * P = 0.0221. Bonferroni post hoc; wild-type versus Mecp2 KO: Arrdc2, ** P = 0.0028; Dusp4, *** P = 0.0003; Klf10, ** P = 0.0053; Tle1, ** P = 0.0037; Bdnf, * P = 0.0307; Nr4a1, * P = 0.0231; wild-type versus IgG: Arrdc2, ** P = 0.0051; Dusp4, *** P = 0.0001; Klf10, ** P = 0.0012; Tle1, ** P = 0.0017; Bdnf, ** P = 0.0080; Nr4a1, * P = 0.0410; n = 4, 4, 4 mice. (e) ChIP of H4K12ac and IgG followed by qPCR analysis at the promoters of Arrdc2, Dusp4, Klf10, Tle1, Bdnf, and Nr4a1 in hippocampal CA1 region of control and Hdac3 cKO mice (% input); one-way ANOVA; Arrdc2, F(2,6) = 18.79, ** P = 0.0026; Dusp4, F(2,6) = 7.802, * P = 0.0214; Klf10, F(2,6) = 10.09, ** P = 0.0120; Tle1, F(2,6) = 6.464, * P = 0.0318; Bdnf, F(2,6) = 8.743, * P = 0.0167; Nr4a1, F(2,6) = 5.209, * P = 0.0488. Bonferroni post hoc; Control versus Hdac3 cKO: Arrdc2, P = 0.5511; Dusp4, P > 0.99; Klf10, P = 0.4278; Tle1, P > 0.99; Bdnf, P > 0.99; Nr4a1, P > 0.99; Control versus IgG: Arrdc2, ** P = 0.0023; Dusp4, * P = 0.0168; Klf10, * P = 0.0478; Tle1, * P = 0.0310; Bdnf, * P = 0.0245; Nr4a1, * P = 0.0448; n = 3, 3, 3 mice. (f) ChIP of H3K9ac and IgG followed by qPCR analysis at the promoters of Arrdc2, Dusp4, Klf10, Tle1, Bdnf, and Nr4a1 in hippocampal CA1 region of control and Hdac3 cKO mice (% input); one-way ANOVA; Arrdc2, F(2,5) = 7.810, * P = 0.0290; Dusp4, F(2,5) = 18.34, ** P = 0.0050; Klf10, F(2,5) = 8.792, * P = 0.0231; Tle1, F(2,5) = 9.315, * P = 0.0206; Bdnf, F(2,5) = 43.53, * P = 0.0007; Nr4a1, F(2,5) = 30.06, ** P = 0.0016. Bonferroni post hoc; Control versus Hdac3 cKO: Arrdc2, P > 0.99; Dusp4, P > 0.99; Klf10, P > 0.99; Tle1, P > 0.99; Bdnf, P = 0.8642; Nr4a1, P = 0.9790; Control versus IgG: Arrdc2, * P = 0.0317; Dusp4, ** P = 0.0058; Klf10, * P = 0.0248; Tle1, * P = 0.0318; Bdnf, *** P = 0.0007; Nr4a1, ** P = 0.0016; n = 3, 3, 2 mice. All values are mean ± s.e.m.
