TY  - JOUR
A1  - Hennig, Thomas
A1  - Michalski, Marco
A1  - Rutkowski, Andrzej J.
A1  - Djakovic, Lara
A1  - Whisnant, Adam W.
A1  - Friedl, Marie-Sophie
A1  - Jha, Bhaskar Anand
A1  - Baptista, Marisa A. P.
A1  - L'Hernault, Anne
A1  - Erhard, Florian
A1  - Dölken, Lars
A1  - Friedel, Caroline C.
T1  - HSV-1-induced disruption of transcription termination resembles a cellular stress response but selectively increases chromatin accessibility downstream of genes
JF  - PLoS Pathogens
N2  - Lytic herpes simplex virus 1 (HSV-1) infection triggers disruption of transcription termination (DoTT) of most cellular genes, resulting in extensive intergenic transcription. Similarly, cellular stress responses lead to gene-specific transcription downstream of genes (DoG). In this study, we performed a detailed comparison of DoTT/DoG transcription between HSV-1 infection, salt and heat stress in primary human fibroblasts using 4sU-seq and ATAC-seq. Although DoTT at late times of HSV-1 infection was substantially more prominent than DoG transcription in salt and heat stress, poly(A) read-through due to DoTT/DoG transcription and affected genes were significantly correlated between all three conditions, in particular at earlier times of infection. We speculate that HSV-1 either directly usurps a cellular stress response or disrupts the transcription termination machinery in other ways but with similar consequences. In contrast to previous reports, we found that inhibition of Ca\(^{2+}\) signaling by BAPTA-AM did not specifically inhibit DoG transcription but globally impaired transcription. Most importantly, HSV-1-induced DoTT, but not stress-induced DoG transcription, was accompanied by a strong increase in open chromatin downstream of the affected poly(A) sites. In its extent and kinetics, downstream open chromatin essentially matched the poly(A) read-through transcription. We show that this does not cause but rather requires DoTT as well as high levels of transcription into the genomic regions downstream of genes. This raises intriguing new questions regarding the role of histone repositioning in the wake of RNA Polymerase II passage downstream of impaired poly(A) site recognition.
KW  - DNA transcription
KW  - dogs
KW  - thermal stresses
KW  - chromatin
KW  - histones
KW  - gene expression
KW  - cellular stress responses
KW  - transcriptional termination
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176350
VL  - 14
IS  - 3
ER  - 
TY  - JOUR
A1  - Djakovic, Lara
A1  - Hennig, Thomas
A1  - Reinisch, Katharina
A1  - Milić, Andrea
A1  - Whisnant, Adam W.
A1  - Wolf, Katharina
A1  - Weiß, Elena
A1  - Haas, Tobias
A1  - Grothey, Arnhild
A1  - Jürges, Christopher S.
A1  - Kluge, Michael
A1  - Wolf, Elmar
A1  - Erhard, Florian
A1  - Friedel, Caroline C.
A1  - Dölken, Lars
T1  - The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes
JF  - Nature Communications
N2  - 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.
KW  - herpes virus
KW  - transcription
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358161
VL  - 14
ER  -