p300‐Dependent acetylation of histone H3 is required for epidermal growth factor receptor (EGFR)‐mediated high‐mobility group protein A2 (HMGA2) transcription in SUN‐368 cells. A, Epidermal growth factor (EGF) treatment induced a significant increase in H3‐K9 acetylation in SNU‐368 cells, ***P < .001, one‐way ANOVA, n = 6 per group. B, Knockdown of p300 reversed EGF‐induced H3‐K9 acetylation in SNU‐368 cells. C, control; E, EGF; #1, shp300#1; #2, shp300#2. **P < .01, ***P < .001, one‐way ANOVA, n = 5 per group. C, Expression of the phosphorylation‐mimic p300 S1834D mutant induced a higher expression of H3‐K9 acetylation in SNU‐368 cells. ***P < .001, one‐way ANOVA, n = 5 per group. Reconstituted expression of RNAi‐resistant histone H3‐K9R abrogated EGF‐induced mRNA (D) and protein (E) expression of HMGA2 in endogenous H3‐depleted SNU‐368 cells. ***P < .001, one‐way ANOVA, n = 5 per group. F, ChIP analysis shows that EGF treatment resulted in enhanced H3‐K9 acetylation at the HMGA2 promoter region 1 and region 2 in SNU‐368 cells. ***P < .01, two‐tailed unpaired t test, n = 5 per group