Fig. 7: m6A regulates mRNA stability of CBP and p300.
a, m6A-meRIP-qPCR of CBP and p300 in Mettl14-KO versus control E14.5 NSCs. One-way ANOVA (n = 3 independent experiments for all experimental groups; CBP, P = 1.08 × 10–6, F(2, 6) = 289.4; p300, P = 3.961 × 10–7, F(2, 6) = 405.5) followed by Bonferroni’s post hoc test (CBP, WT versus KO, P = 1.697 × 10–6, 95% C.I. = 16.18–21.63, WT versus Het, P = 0.9999, 95% C.I. = –3.13–2.316; p300, WT versus KO, P = 1.113 × 10–6, 95% C.I. = 21.47–28.12, WT versus Het, P = 0.0086, 95% C.I. = –8.32 to –1.667). b, RT-qPCR of CBP and p300 transcripts in E14.5 NSCs cultured for 7 d in vitro; one-way ANOVA (n = 21 (WT), 33 (KO), or 21 (Het) independent experiments for all experimental groups; CBP, P = 2.380 × 10–21, F(2, 72) = 98.64; p300, P = 2.751 × 10–9, F(2, 72) = 26.24) followed by Bonferroni’s post hoc test (CBP, WT versus KO, P = 1.306 × 10–19, 95% C.I. = –1.252 to –0.8628, WT versus Het, P = 0.3029, 95% C.I. = –0.3512–0.07886; p300, WT versus KO, P = 5.254 × 10–9, 95% C.I. = –0.6356 to –0.3153, WT versus Het, P = 0.2011, 95% C.I. = –0.3058–0.04839). c, RT-qPCR of CBP and p300 transcripts in ActD-treated E14.5 NSCs. P values are generated by two-way ANOVA (n = 3 independent experiments for all experimental groups; CBP, P = 1.262 × 10–11, F(1, 12) = 602.5; p300, P = 8.738 × 10–10, F(1, 12) = 291.7) followed by Bonferroni’s post hoc test (CBP, 0 h, P = 0.9999, 95% C.I. = –0.05658–0.05658, 3 h, P = 1.714 × 10–8, 95% C.I. = –0.3518 to –0.2386, 6 h, P = 7.954 × 10–12, 95% C.I. = –0.6268 to –0.5136; p300, 0 h, P = 0.9999, 95% C.I. = –0.06777–0.06777, 3 h, P = 1.988 × 10–7, 95% C.I. = –0.3522 to –0.2167, 6 h, P = 1.50564 × 10–9, 95% C.I. = –0.5046 to –0.3691). d, A model in which m6A loss alters histone modifications partly through regulation of mRNA stability of histone modifiers, and altered histone modifications aberrantly repress proliferation-related genes and activate differentiation-related genes, resulting in loss of NSC ground state. Graphs represent the mean ± s.d. Dots represent data from individual data points. The horizontal lines in the box plots indicate medians, the box limits indicate first and third quantiles, and the vertical whisker lines indicate minimum and maximum values. ****P < 0.0001.
