Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Versbacher Straße 7, 97078, Würzburg, Germany.
Institute of Informatics, Ludwig-Maximilians-Universität München, Amalienstr. 17, 80333, Munich, Germany.
Nat Commun. 2023 Jul 31;14(1):4591. doi: 10.1038/s41467-023-40217-w.
Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection.
单纯疱疹病毒 1（HSV-1）感染和应激反应会破坏 RNA 聚合酶 II（Pol II）的转录终止。在 HSV-1 感染中，但不是在盐或热应激时，这种情况伴随着基因下游染色质可及性的急剧增加。在这里，我们表明，当病毒 ICP27 蛋白破坏转录终止时，HSV-1 的早期即刻蛋白 ICP22 既是必需的也是充分的，可诱导下游开放染色质区域（dOCR）。这伴随着受影响基因下游明显的 ICP22 依赖性组蛋白丢失，与 Pol II 之后组蛋白重新定位受损一致。有效的 ICP22 相互作用组蛋白伴侣 FACT 的敲低不足以在 ΔICP22 感染中诱导 dOCR，但会增加野生型 HSV-1 感染中的 dOCR 诱导。有趣的是，这伴随着基因体内染色质可及性的显著增加。我们提出了一个模型，其中基因下游 Pol II 组成的变构变化和 ICP22 介导的对 FACT 活性的干扰解释了在 HSV-1 感染中 Pol II 之后基因下游组蛋白重新定位的不同程度的损伤。
