Fig. 6: H3K27ac inhibitor C646 and H3K27me3 inhibitor GSK343 rescue aberrant gene expression in KO versus nondeleted NSCs. | Nature Neuroscience

Fig. 6: H3K27ac inhibitor C646 and H3K27me3 inhibitor GSK343 rescue aberrant gene expression in KO versus nondeleted NSCs.

From: N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications

Fig. 6

a, H3K27ac ChIP-qPCR showing increased promoter and enhancer H3K27ac of Kif26a, Gas7 and Pdgfrb genes in E14.5 Mettl14-KO versus nondeleted NSCs. n = 4 independent experiments for all experimental groups; two-tailed unpaired t-test (Kif26a, P = 0.0006, t = 6.568, df = 6, 95% C.I. = 9.594–20.99; Gas7, P = 0.00013, t = 8.638, df = 6, 95% C.I. = 17.41–31.16; Pdgfrb, P = 0.0002, t = 8.395, df = 6, 95% C.I. = 9.27–16.9). b, RT-qPCR showing increased expression of Kif26a, Gas7 and Pdgfrb genes in E14.5 Mettl14-KO versus nondeleted NSCs. n = 3 independent experiments for all experimental groups; two-tailed unpaired t-test (Kif26a, P = 0.0002, t = 12.71, df = 4, 95% C.I. = 25.01–38.99; Gas7, P = 0.0002, t = 12.46, df = 4, 95% C.I. = 11.41–17.95; Pdgfrb, P = 0.0008, t = 9.08, df = 4, 95% C.I. = 2.957–5.563). c, RT-qPCR showing decreased expression of Kif26a, Gas7 and Pdgfrb genes in E14.5 Mettl14-KO versus nondeleted NSCs treated with H3K27ac inhibitor C646. One-way ANOVA (n = 3 independent experiments for all experimental groups; Kif26a, P = 0.0015, F(2, 6) = 23.04; Gas7, P = 0.0027, F(2, 6) = 18.67; Pdgfrb, P = 8.449 × 10–7, F(2, 6) = 314.3) followed by Bonferroni’s post hoc test (Kif26a, c versus 0.625, P = 0.0041, 95% C.I. = 6.126–22.47, c versus 1.25, P = 0.0014, 95% C.I. = 9.393–25.73; Gas7, c versus 0.625, P = 0.045, 95% C.I. = 0.05735–4.229, c versus 1.25, P = 0.0018, 95% C.I. = 2.207–6.379; Pdgfrb, c versus 0.625, P = 1.431 × 10–5, 95% C.I. = 1.75–2.663, c versus 1.25, P = 5.418 × 10–7, 95% C.I. = 3.384–4.296). d, H3K27me3 ChIP-qPCR showing increased H3K27me3 at promoters of Egr2 and Egr3 genes in E14.5 Mettl14-KO versus nondeleted NSCs. n = 4 independent experiments for all experimental groups; two-tailed unpaired t-test (Egr2, P = 0.0016, t = 5.463, df = 6, 95% C.I. = 5.412–14.19; Egr3, P = 0.0010, t = 5.928, df = 6, 95% C.I. = 5.007–12.05). e, RT-qPCR showing decreased expression of Egr2 and Egr3 genes in E14.5 Mettl14-KO versus nondeleted NSCs. n = 3 independent experiments for all experimental groups; two-tailed unpaired t-test (Egr2, P = 0.0052, t = 5.603, df = 4, 95% C.I. = –0.3789 to –0.1278; Egr3, P = 0.0009, t = 10.67, df = 4, 95% C.I. = –0.7855 to –0.4612). f, RT-qPCR showing increased expression of Egr2 and Egr3 genes in E14.5 Mettl14-KO versus nondeleted NSCs treated with H3K27me3 inhibitor GSK343. One-way ANOVA (n = 3 independent experiments for all experimental groups; Egr2, P = 0.0003, F(2, 6) = 44.49; Egr3, P = 0.01, F(2, 6) = 10.94) followed by Bonferroni’s post hoc test (Egr2, c versus 0.625, P = 0.0007, 95% C.I. = –0.4826 to –0.2041, c versus 1.25, P = 0.0002, 95% C.I. = –0.5526 to –0.2741; Egr3, c versus 0.625, P = 0.0519, 95% C.I. = –0.5627–0.002676, c versus 1.25, P = 0.0072, 95% C.I. = –0.7227 to –0.1573). Graphs represent the mean ± s.d. Dots represent data from individual data points. ns, non-significant. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

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