title: Association of the interferon-β gene with pericentromeric heterochromatin is dynamically regulated during virus infection through a YY1-dependent mechanism.
abstract: Nuclear architecture as well as gene nuclear positioning can modulate gene expression. In this work, we have analyzed the nuclear position of the interferon-β (IFN-β) locus, responsible for the establishment of the innate antiviral response, with respect to pericentromeric heterochromatin (PCH) in correlation with virus-induced IFN-β gene expression. Experiments were carried out in two different cell types either non-infected (NI) or during the time course of three different viral infections. In NI cells, we showed a monoallelic IFN-β promoter association with PCH that strongly decreased after viral infection. Dissociation of the IFN-β locus away from these repressive regions preceded strong promoter transcriptional activation and was reversible within 12  h after infection. No dissociation was observed after infection with a virus that abnormally maintained the IFN-β gene in a repressed state. Dissociation induced after virus infection specifically targeted the IFN-β locus without affecting the general structure and nuclear distribution of PCH clusters. Using cell lines stably transfected with wild-type or mutated IFN-β promoters, we identified the proximal region of the IFN-β promoter containing YY1 DNA-binding sites as the region regulating IFN-β promoter association with PCH before as well as during virus infection.
authors.affiliation: Régulation de la Transcription et Maladies Génétiques, CNRS FRE3235, Université Paris Descartes, 45 rue des Saints Pères, 75270, Paris cedex 06, France.
authors.forename: T
authors.initials: T
authors.lastname: Josse
authors.forename: H
authors.initials: H
authors.lastname: Mokrani-Benhelli
authors.forename: R
authors.initials: R
authors.lastname: Benferhat
authors.forename: E
authors.initials: E
authors.lastname: Shestakova
authors.forename: Z
authors.initials: Z
authors.lastname: Mansuroglu
authors.forename: H
authors.initials: H
authors.lastname: Kakanakou
authors.forename: A
authors.initials: A
authors.lastname: Billecocq
authors.forename: M
authors.initials: M
authors.lastname: Bouloy
authors.forename: Eliette
authors.initials: E
authors.lastname: Bonnefoy
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004276:DNA, Satellite / Q000032:analysis; D006570:Heterochromatin / Q000737:chemistry*; D016899:Interferon-beta / Q000235:genetics*; D051379:Mice; D009522:Newcastle disease virus / Q000502:physiology; D011401:Promoter Regions, Genetic; D012296:Rift Valley fever virus / Q000502:physiology; D015533:Transcriptional Activation; D050986:YY1 Transcription Factor / Q000378:metabolism*
chemical_list: D004276:DNA, Satellite; D006570:Heterochromatin; D050986:YY1 Transcription Factor; D016899:Interferon-beta