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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40217-w |
| _version_ | 1797752701417684992 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Lara Djakovic |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T17:07:15Z |
| format | Article |
| id | doaj.art-88c94da7658643c8abd946d207f3dd82 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-12T17:07:15Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-88c94da7658643c8abd946d207f3dd822023-08-06T11:19:28ZengNature PortfolioNature Communications2041-17232023-07-0114111710.1038/s41467-023-40217-wThe HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genesLara Djakovic0Thomas Hennig1Katharina Reinisch2Andrea Milić3Adam W. Whisnant4Katharina Wolf5Elena Weiß6Tobias Haas7Arnhild Grothey8Christopher S. Jürges9Michael Kluge10Elmar Wolf11Florian Erhard12Caroline C. Friedel13Lars Dölken14Institute for Virology and Immunobiology, Julius-Maximilians-University WürzburgInstitute for Virology and Immunobiology, Julius-Maximilians-University WürzburgInstitute of Informatics, Ludwig-Maximilians-Universität MünchenInstitute for Virology and Immunobiology, Julius-Maximilians-University WürzburgInstitute for Virology and Immunobiology, Julius-Maximilians-University WürzburgInstitute for Virology and Immunobiology, Julius-Maximilians-University WürzburgInstitute of Informatics, Ludwig-Maximilians-Universität MünchenInstitute for Virology and Immunobiology, Julius-Maximilians-University WürzburgInstitute for Virology and Immunobiology, Julius-Maximilians-University WürzburgInstitute for Virology and Immunobiology, Julius-Maximilians-University WürzburgInstitute of Informatics, Ludwig-Maximilians-Universität MünchenCancer Systems Biology Group, Theodor Boveri Institute, University of WürzburgInstitute for Virology and Immunobiology, Julius-Maximilians-University WürzburgInstitute of Informatics, Ludwig-Maximilians-Universität MünchenInstitute for Virology and Immunobiology, Julius-Maximilians-University WürzburgAbstract 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.https://doi.org/10.1038/s41467-023-40217-w |
| spellingShingle | 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 The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes Nature Communications |
| title | The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes |
| title_full | The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes |
| title_fullStr | The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes |
| title_full_unstemmed | The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes |
| title_short | The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes |
| title_sort | hsv 1 icp22 protein selectively impairs histone repositioning upon pol ii transcription downstream of genes |
| url | https://doi.org/10.1038/s41467-023-40217-w |
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