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.

中文翻译：

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朊病毒表观遗传开关建立活跃的染色质状态。

组蛋白的共价修饰对于发育、从共同的基因序列建立独特的功能性染色质结构域至关重要。尽管受抑制的染色质具有很强的遗传性，但尚未描述促进激活结构域遗传的机制。在这里，我们报告 Set3C 组蛋白脱乙酰酶支架 Snt1 可以充当朊病毒，驱动激活染色质状态的出现和跨代遗传。这种朊病毒，我们将表达的亚端粒信息称为 [ESI+]，是由细胞周期停滞时短暂的 Snt1 磷酸化触发的。一旦接合，朊病毒就会重塑 Snt1 和 Set3C 复合体的活性，招募 RNA pol II 并干扰 Rap1 结合，从而激活原本受到抑制的亚端粒域中的基因。这种转录状态赋予了对环境压力的广泛抵抗力，包括抗真菌药物。总而言之，我们的结果建立了一种强大的方法，朊病毒可以通过该方法促进激活染色质状态的遗传，从而提供适应性益处。