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Parallel G-quadruplexes recruit the HSV-1 transcription factor ICP4 to promote viral transcription in herpes virus-infected human cells.
- Source :
-
Communications biology [Commun Biol] 2021 Apr 30; Vol. 4 (1), pp. 510. Date of Electronic Publication: 2021 Apr 30. - Publication Year :
- 2021
-
Abstract
- G-quadruplexes (G4s) are four-stranded nucleic acid structures abundant at gene promoters. They can adopt several distinctive conformations. G4s have been shown to form in the herpes simplex virus-1 (HSV-1) genome during its viral cycle. Here by cross-linking/pull-down assay we identified ICP4, the major HSV-1 transcription factor, as the protein that most efficiently interacts with viral G4s during infection. ICP4 specific and direct binding and unfolding of parallel G4s, including those present in HSV-1 immediate early gene promoters, induced transcription in vitro and in infected cells. This mechanism was also exploited by ICP4 to promote its own transcription. Proximity ligation assay allowed visualization of G4-protein interaction at the single selected G4 in cells. G4 ligands inhibited ICP4 binding to G4s. Our results indicate the existence of a well-defined G4-viral protein network that regulates the productive HSV-1 cycle. They also point to G4s as elements that recruit transcription factors to activate transcription in cells.
- Subjects :
- Bone Neoplasms genetics
Bone Neoplasms pathology
Bone Neoplasms virology
DNA Replication
Herpes Simplex genetics
Herpes Simplex virology
Humans
Immediate-Early Proteins genetics
Osteosarcoma genetics
Osteosarcoma pathology
Tumor Cells, Cultured
G-Quadruplexes
Herpes Simplex complications
Herpesvirus 1, Human genetics
Immediate-Early Proteins metabolism
Osteosarcoma virology
Promoter Regions, Genetic
Viral Transcription
Subjects
Details
- Language :
- English
- ISSN :
- 2399-3642
- Volume :
- 4
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Communications biology
- Publication Type :
- Academic Journal
- Accession number :
- 33931711
- Full Text :
- https://doi.org/10.1038/s42003-021-02035-y