Melatonin induces histone hyperacetylation in the rat brain

We have reported that melatonin induces histone hyperacetylation in mouse neural stem cells, suggesting an epigenetic role for this pleiotropic hormone. To support such a role, it is necessary to demonstrate that melatonin produces similar effects in vivo. Histone acetylation, following chronic treatment with melatonin (4μg/ml in drinking water for 17 days), was examined by western blotting in selected rat brain regions. Melatonin induced significant increases in histone H3 and histone H4 acetylation in the hippocampus. Histone H4 was also hyperacetylated in the striatum, but there were no significant changes in histone H3 acetylation in this brain region. No significant changes in the acetylation of either histone H3 or H4 were observed in the midbrain and cerebellum. An examination of kinase activation, which may be related to these changes, revealed that melatonin treatment increased the levels of phospho-ERK (extracellular signal-regulated kinase) in the hippocampus and striatum, but phospho-Akt (protein kinase B) levels were unchanged. These findings suggest that chromatin remodeling and associated changes in the epigenetic regulation of gene expression underlie the multiple physiological effects of melatonin.