Neural stem cell quiescence is actively maintained by the epigenome

Homeostasis and repair of the nervous system is maintained by a population of resident neural stem cells (NSCs) retained in a state of reversible cell cycle arrest called quiescence. quiescent NSCs can resume proliferation in response to different physiological stimuli, such as diet or injury. Reactivation of NSCs requires changes in gene expression, much of which is regulated at the epigenomic level. We mapped, comprehensively and in vivo, the dynamic epigenomic changes in NSC chromatin during stem cell quiescence and reactivation in Drosophila. Contrary to expectations, we found that chromatin accessibility is increased in quiescent NSCs, remodelling extensively within both euchromatin and heterochromatin. Surprisingly, genes crucial for cell cycle progression are repressed whilst remaining within permissive H3K36me3-bound euchromatin. At the same time, genes necessary for cell-cell communication are derepressed by eviction of histone H1 and transition to a SWI/SNF-enriched active state. Our results reveal global expansion of accessible chromatin in quiescent NSCs without concomitant activation of transcription. Strikingly, this process reverses upon reactivation, indicating that opening of chromatin is a quiescence-specific event.