@Article{Djakovic2023, author = {Djakovic, Lara and Hennig, Thomas and Reinisch, Katharina and Milic, Andrea and Whisnant, Adam W. and Wolf, Katharina and Elena Weiß and Haas, Tobias and Grothey, Arnhild and Jürges, Christopher S. and Kluge, Michael and Wolf, Elmar and Erhard, Florian and Friedel, Caroline C. and Dölken, Lars}, journal = {Nature communications}, title = {The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes.}, year = {2023}, issn = {2041-1723}, month = jul, pages = {4591}, volume = {14}, 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 ?ICP22 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.}, chemicals = {Histones, Viral Proteins, Chromatin, ICP22 protein, human herpesvirus 1, Immediate-Early Proteins}, citation-subset = {IM}, completed = {2023-08-03}, country = {England}, doi = {10.1038/s41467-023-40217-w}, issn-linking = {2041-1723}, issue = {1}, keywords = {Humans; Histones, metabolism; Herpesvirus 1, Human, genetics; Transcription, Genetic; Viral Proteins, genetics, metabolism; Herpes Simplex, genetics; Chromatin, genetics, metabolism; Immediate-Early Proteins, genetics, metabolism}, nlm-id = {101528555}, owner = {NLM}, pii = {4591}, pmc = {PMC10390501}, pmid = {37524699}, pubmodel = {Electronic}, pubstate = {epublish}, revised = {2023-08-04}, }