RESUMO
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 that facilitates inheritance of an activated domain has been described. 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. Altogether, our results establish a robust means by which a prion can facilitate inheritance of an activated chromatin state to provide adaptive benefit.
Assuntos
Cromatina/genética , Histona Desacetilases/genética , Proteínas Nucleares/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Ligação a Telômeros/genética , Fatores de Transcrição/genética , Pontos de Checagem do Ciclo Celular/genética , Código das Histonas/genética , Histonas/genética , Fosforilação/genética , Príons/genética , RNA Polimerase II/genética , Saccharomyces cerevisiae , Complexo Shelterina , Telômero/genética , Transcrição GênicaRESUMO
To survive, organisms must orchestrate competing biochemical and regulatory processes in time and space. Recent work has suggested that the underlying chemical properties of some biomolecules allow them to self-organize and that life may have exploited this property to organize biochemistry in space and time. Such phase separation is ubiquitous, particularly among the many regulatory proteins that harbor prion-like intrinsically disordered domains. And yet, despite evident regulation by post-translational modification and myriad other stimuli, the biological significance of many phase-separated compartments remains uncertain. Many potential functions have been proposed, but far fewer have been demonstrated. A burgeoning subfield at the intersection of cell biology and polymer physics has defined the biophysical underpinnings that govern the genesis and stability of these particles. The picture is complex: many assemblies are composed of multiple proteins that each have the capacity to phase separate. Here, we briefly discuss this foundational work and survey recent efforts combining targeted biochemical perturbations and quantitative modeling to specifically address the diverse roles that phase separation processes may play in biology.