title: Knockdown of hDaxx in normally non-permissive undifferentiated cells does not permit human cytomegalovirus immediate-early gene expression.
abstract: The cellular protein human Daxx (hDaxx), a component of nuclear domain 10 structures, is known to mediate transcriptional repression of human cytomegalovirus immediate-early (IE) gene expression upon infection of permissive cell types, at least in part, by regulation of chromatin structure around the major IE promoter (MIEP). As it is now clear that differentiation-dependent regulation of the MIEP also plays a pivotal role in the control of latency and reactivation, we asked whether hDaxx-mediated repression is involved in differentiation-dependent MIEP regulation. We show that downregulation of hDaxx by using small interfering RNA technology in undifferentiated NT2D1 cells does not permit expression of viral IE genes, nor does it result in changes in chromatin structure around the MIEP. Viral IE gene expression is only observed upon cellular differentiation, suggesting little involvement of hDaxx in the regulation of the viral MIEP in undifferentiated cells.
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Groves
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
authors.forename: John H
authors.initials: JH
authors.lastname: Sinclair
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000956:Antigens, Viral / Q000096:biosynthesis; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D056970:Co-Repressor Proteins; D003587:Cytomegalovirus / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014775:Virus Activation / Q000235:genetics / Q000502:physiology; D017735:Virus Latency / Q000235:genetics / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000956:Antigens, Viral; D002843:Chromatin; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D017874:Immediate-Early Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C044582:immediate-early proteins, cytomegalovirus