RESUMEN
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.
Asunto(s)
Cromatina/genética , Histona Desacetilasas/genética , Proteínas Nucleares/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Unión a Telómeros/genética , Factores de Transcripción/genética , Puntos de Control del Ciclo Celular/genética , Código de Histonas/genética , Histonas/genética , Fosforilación/genética , Priones/genética , ARN Polimerasa II/genética , Saccharomyces cerevisiae , Complejo Shelterina , Telómero/genética , Transcripción GenéticaRESUMEN
Epigenetics refers to changes in phenotype that are not rooted in DNA sequence. This phenomenon has largely been studied in the context of chromatin modification. Yet many epigenetic traits are instead linked to self-perpetuating changes in the individual or collective activity of proteins. Most such proteins are prions (e.g., [PSI+], [URE3], [SWI+], [MOT3+], [MPH1+], [LSB+], and [GAR+]), which have the capacity to adopt at least one conformation that self-templates over long biological timescales. This allows them to serve as protein-based epigenetic elements that are readily broadcast through mitosis and meiosis. In some circumstances, self-templating can fuel disease, but it also permits access to multiple activity states from the same polypeptide and transmission of that information across generations. Ensuing phenotypic changes allow genetically identical cells to express diverse and frequently adaptive phenotypes. Although long thought to be rare, protein-based epigenetic inheritance has now been uncovered in all domains of life.
Asunto(s)
Herencia/fisiología , Priones/metabolismo , Priones/fisiología , Animales , Epigénesis Genética/fisiología , Epigenómica/métodos , Humanos , Meiosis , Mitosis , Fenotipo , Proteínas/metabolismoRESUMEN
Over the past few years, interest in chromatin and its evolution has grown. To further advance these interests, we organized a workshop with the support of The Company of Biologists to debate the current state of knowledge regarding the origin and evolution of chromatin. This workshop led to prospective views on the development of a new field of research that we term 'EvoChromo'. In this short Spotlight article, we define the breadth and expected impact of this new area of scientific inquiry on our understanding of both chromatin and evolution.
Asunto(s)
Cromatina/genética , Evolución Molecular , Animales , Genoma , HumanosRESUMEN
Bacillus niacini is a member of a small yet diverse group of bacteria able to catabolize nicotinic acid. We report here the availability of a draft genome for B. niacini, which we will use to understand the evolution of its namesake phenotype, which appears to be unique among the species in its phylogenetic neighborhood.