Neuronal activity modifies the chromatin accessibility landscape in the adult brain

Neuronal activity-induced gene expression modulates the function and plasticity of the nervous system. It is unknown whether and to what extent neuronal activity may trigger changes in chromatin accessibility, a major mode of epigenetic regulation of gene expression. Here we compared chromatin accessibility landscapes of adult mouse dentate granule neurons in vivo before and after synchronous neuronal activation using ATAC-seq. We found widespread, genome-wide changes one hour after activation, with enrichment of gained-open sites at active enhancer regions and at binding sites for AP1 complex components, including cFos. Some changes remain stable for at least twenty-four hours. Functional analysis further implicates a critical role of cFos in initiating, but not maintaining, neuronal activity-induced chromatin opening. Our results reveal dynamic changes of chromatin accessibility in the adult mammalian brain and suggest an epigenetic mechanism by which transient neuronal activation leads to dynamic changes in gene expression via modifying chromatin accessibility.