美国斯坦福大学医学院Daniel F. Jarosz研究组发现，蛋白质侵染因子表观遗传开关建立了活跃的染色质状态。论文在线发表在2020年2月27日的《细胞》上。

研究人员发现Set3C组蛋白去乙酰化酶支架蛋白Snt1可以作为蛋白质侵染因子，促进活化态染色质的出现和跨代遗传。研究人员将此蛋白质侵染因子命名为[ESI +]其表达亚端粒信息并且这些蛋白质侵染因子是由细胞周期停滞时Snt1瞬时磷酸化诱导产生的。

一旦蛋白质侵染因子参与，其会重塑Snt1和Set3C复合体的活性，招募RNA pol II并干扰Rap1与激活基因的结合，否则这些基因则会受到亚端粒结构域的抑制。这种转录状态赋予细胞广泛抗环境压力的能力，包括抗真菌药。

总而言之，该研究揭示了一种强有力的方式，蛋白质侵染因子可以通过该方法促进活化染色质状态的遗传，从而提供有利的适应性。

据介绍，组蛋白共价修饰对于从基本遗传序列中建立独特的功能性染色质结构域至关重要。尽管阻抑性染色质是稳定遗传的，但尚未揭示促进活化域遗传的机制。

附：英文原文

Title: A Prion Epigenetic Switch Establishes an Active Chromatin State

Author: Zachary H. Harvey, Anupam K. Chakravarty, Raymond A. Futia, Daniel F. Jarosz

Issue&Volume: 2020-02-27

Abstract: Covalent modifications to histones are essential for development, establishing distinctand functional chromatin domains from a common genetic sequence. Whereas repressedchromatin is robustly inherited, no mechanism that facilitates inheritance of an activateddomain has been described. Here, we report that the Set3C histone deacetylase scaffoldSnt1 can act as a prion that drives the emergence and transgenerational inheritanceof an activated chromatin state. This prion, which we term [ESI+] for expressed sub-telomeric information, is triggered by transient Snt1 phosphorylationupon cell cycle arrest. Once engaged, the prion reshapes the activity of Snt1 andthe Set3C complex, recruiting RNA pol II and interfering with Rap1 binding to activategenes in otherwise repressed sub-telomeric domains. This transcriptional state confersbroad resistance to environmental stress, including antifungal drugs. Altogether,our results establish a robust means by which a prion can facilitate inheritance ofan activated chromatin state to provide adaptive benefit.

DOI: 10.1016/j.cell.2020.02.014

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30158-6