title: CTCF interacts with the lytic HSV-1 genome to promote viral transcription.
abstract: CTCF is an essential chromatin regulator implicated in important nuclear processes including in nuclear organization and transcription. Herpes Simplex Virus-1 (HSV-1) is a ubiquitous human pathogen, which enters productive infection in human epithelial and many other cell types. CTCF is known to bind several sites in the HSV-1 genome during latency and reactivation, but its function has not been defined. Here, we report that CTCF interacts extensively with the HSV-1 DNA during lytic infection by ChIP-seq, and its knockdown results in the reduction of viral transcription, viral genome copy number and virus yield. CTCF knockdown led to increased H3K9me3 and H3K27me3, and a reduction of RNA pol II occupancy on viral genes. Importantly, ChIP-seq analysis revealed that there is a higher level of CTD Ser2P modified RNA Pol II near CTCF peaks relative to the Ser5P form in the viral genome. Consistent with this, CTCF knockdown reduced the Ser2P but increased Ser5P modified forms of RNA Pol II on viral genes. These results suggest that CTCF promotes HSV-1 lytic transcription by facilitating the elongation of RNA Pol II and preventing silenced chromatin on the viral genome.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Kunming 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Beijing 100101, China.
authors.forename: Fengchao
authors.initials: F
authors.lastname: Lang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Kunming 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Beijing 100101, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Vladimirova
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Kunming 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Beijing 100101, China.
authors.forename: Benxia
authors.initials: B
authors.lastname: Hu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Kunming 650223, China.
authors.forename: Guijun
authors.initials: G
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Kunming 650223, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Vikrant
authors.initials: V
authors.lastname: Singh
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Kunming 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Beijing 100101, China.
authors.forename: Danfeng
authors.initials: D
authors.lastname: Lu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Kunming 650223, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Li
authors.affiliation: Biology &Chemistry Engineering College, Panzhihua University, Panzhihua, Sichuan 617000, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Han
authors.affiliation: Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: J M A S P
authors.initials: JM
authors.lastname: Wickramasinghe
authors.affiliation: Department of Biology, Arcadia University, Glenside, PA 19038, USA.
authors.forename: Sheryl T
authors.initials: ST
authors.lastname: Smith
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China.|Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming, Kunming 650118, China.
authors.forename: Qihan
authors.initials: Q
authors.lastname: Li
authors.affiliation: Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Lieberman
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Fraser
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Kunming 650223, China.
authors.forename: Jumin
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor / Q000378:metabolism*; D002522:Chlorocebus aethiops; D042002:Chromatin Assembly and Disassembly; D016679:Genome, Viral; D057809:HEK293 Cells; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D000076246:CCCTC-Binding Factor; D006657:Histones; D012367:RNA, Viral; D012319:RNA Polymerase II