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

SUBMITTER: Josse T 

PROVIDER: S-EPMC3378888 | biostudies-other | 2012 May

REPOSITORIES: biostudies-other