title: Failure to interact with Brd4 alters the ability of HPV16 E2 to regulate host genome expression and cellular movement.
abstract: The E2 protein of the carcinogen human papillomavirus 16 (HPV16) regulates replication and transcription of the viral genome in association with viral and cellular proteins. Our previous work demonstrated that E2 can regulate transcription from the host genome. E2 can activate transcription from adjacent promoters when located upstream using E2 DNA binding sequences and this activation is dependent upon the cellular protein Brd4; this report demonstrates that a Brd4 binding E2 mutant alters host genome expression differently from wild type E2. Of particular note is that highly down regulated genes are mostly not affected by failure to interact with Brd4 suggesting that the E2-Brd4 interaction is more responsible for the transcriptional activation of host genes rather than repression. Therefore failure to interact efficiently with Brd4, or altered levels of Brd4, would alter the ability of E2 to regulate the host genome and could contribute to determining the outcome of infection.
authors.affiliation: VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USA; University of Glasgow Institute of Infection, Immunology and Inflammation, Glasgow G12 8QQ, UK.
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Gauson
authors.affiliation: VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: University of Glasgow Institute of Infection, Immunology and Inflammation, Glasgow G12 8QQ, UK.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Dornan
authors.affiliation: Institute of Molecular Cell and Systems Biology, University of Glasgow, Glasgow G12 8QQ, UK; Glasgow Polyomics, University of Glasgow, Glasgow, UK.
authors.forename: Pawel
authors.initials: P
authors.lastname: Herzyk
authors.affiliation: VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USA.
authors.forename: Molly
authors.initials: M
authors.lastname: Bristol
authors.affiliation: VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USA; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address: immorgan@vcu.edu.
authors.forename: Iain M
authors.initials: IM
authors.lastname: Morgan
mesh_terms: D018797:Cell Cycle Proteins; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology* / Q000821:virology; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C054855:E2 protein, Human papillomavirus type 16
keywords: Affymetrix; Brd4; Cancer; E2; Exon array; Human papillomavirus