This caused a decrease in H3 and H4 acetylation, resulting in CREB gene repression.259 Treatment with HDAC inhibitors and/or antidepressant drug (e.g., imipramine, fluoxetine) significantly elevated H4K12ac level at the Bdnf promoter in the PFC along with increased Bdnf expression.259,260 Additionally, the latest studies proposed that histone crotonylation play a key role in regulating stress-induced depression. The gene discussed is BDNF; the disease is major depressive disorder.