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

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) upon disrupted transcription termination. This was matched 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 chaperon FACT, though insufficient to induce dOCRs in ΔICP22 infection, increased dOCR induction upon wild-type HSV-1 infection. Interestingly, this was 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 re-positioning in the wake of Pol II observed in HSV-1 infection.