The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes.

Abstract

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.

• Authors: Lara Djakovic, Thomas Hennig, Katharina Reinisch, Andrea Milić, Adam W Whisnant, Katharina Wolf, Elena Weiß, Tobias Haas, Arnhild Grothey, Christopher S Jürges, Michael Kluge, Elmar Wolf, Florian Erhard, Caroline C Friedel, Lars Dölken
• Journal: Nature communications (Nat Commun) Vol. 14 Issue 1 Pg. 4591 (07 31 2023) ISSN: 2041-1723 [Electronic] England
• PMID: 37524699 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• Histones
• Viral Proteins
• Chromatin
• ICP22 protein, human herpesvirus 1
• Immediate-Early Proteins

Topics

• Humans
• Histones (metabolism)
• Herpesvirus 1, Human (genetics)
• Transcription, Genetic
• Viral Proteins (genetics, metabolism)
• Herpes Simplex (genetics)
• Chromatin (genetics, metabolism)
• Immediate-Early Proteins (genetics, metabolism)