Association of the interferon-beta gene with pericentromeric heterochromatin is dynamically regulated during virus infection through a YY1-dependent mechanism

作者：Josse T; Mokrani Benhelli H; Benferhat R; Shestakova E; Mansuroglu Z; Kakanakou H; Billecocq A; Bouloy M; Bonnefoy Eliette^*

来源：Nucleic Acids Research, 2012, 40(10): 4396-4411.

DOI：10.1093/nar/gks050

Nuclear architecture as well as gene nuclear positioning can modulate gene expression. In this work, we have analyzed the nuclear position of the interferon-beta (IFN-beta) locus, responsible for the establishment of the innate antiviral response, with respect to pericentromeric heterochromatin (PCH) in correlation with virus-induced IFN-beta 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-beta promoter association with PCH that strongly decreased after viral infection. Dissociation of the IFN-beta 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-beta gene in a repressed state. Dissociation induced after virus infection specifically targeted the IFN-beta locus without affecting the general structure and nuclear distribution of PCH clusters. Using cell lines stably transfected with wild-type or mutated IFN-beta promoters, we identified the proximal region of the IFN-beta promoter containing YY1 DNA-binding sites as the region regulating IFN-beta promoter association with PCH before as well as during virus infection.

• 出版日期2012-5