A Prion Epigenetic Switch Establishes an Active Chromatin State
79 Pages Posted: 23 Aug 2019 Sneak Peek Status: Under ReviewMore...
Covalent modifications to histones are essential for development, establishing distinct and functional chromatin domains from a common genetic sequence. Whereas repressed chromatin is robustly inherited, no mechanism has been described that facilitates inheritance of an activated domain. Here we report that the Set3C histone deacetylase scaffold Snt1 can act as a prion that drives the emergence, and transgenerational inheritance, of an activated chromatin state. This prion, which we term [ESI+] for expressed sub-telomeric information, is triggered by transient Snt1 phosphorylation upon cell cycle arrest. Once engaged, the prion reshapes the activity of Snt1, and the Set3C complex, recruiting RNA pol II and interfering with Rap1 binding to activate genes in otherwise repressed sub-telomeric domains. This transcriptional state confers broad resistance to environmental stress, including antifungal drugs. Together, our results provide a robust means by which a prion can facilitate inheritance of an activated chromatin state to provide adaptive benefit.
Keywords: Prions, Epigenetics, Stress Response, Chromatin State
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