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A Prion Epigenetic Switch Establishes an Active Chromatin State

79 Pages Posted: 23 Aug 2019 Sneak Peek Status: Under Review

See all articles by Zachary H. Harvey

Zachary H. Harvey

Stanford University - Department of Chemical and Systems Biology

Raymond A. Futia

Stanford University - Department of Biology

Daniel F. Jarosz

Stanford University - Department of Chemical and Systems Biology; Stanford University - Department of Developmental Biology

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Abstract

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

Suggested Citation

Harvey, Zachary H. and Futia, Raymond A. and Jarosz, Daniel F., A Prion Epigenetic Switch Establishes an Active Chromatin State (August 21, 2019). CELL-D-19-02344. Available at SSRN: https://ssrn.com/abstract=3440905 or http://dx.doi.org/10.2139/ssrn.3440905
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Zachary H. Harvey

Stanford University - Department of Chemical and Systems Biology ( email )

Stanford, CA 94305
United States

Raymond A. Futia

Stanford University - Department of Biology ( email )

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States

Daniel F. Jarosz (Contact Author)

Stanford University - Department of Chemical and Systems Biology ( email )

Stanford, CA 94305
United States

Stanford University - Department of Developmental Biology ( email )

Stanford, CA 94305
United States

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