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Nucleic Acids Res ; 40(10): 4396-411, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22287632

RESUMO

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


Assuntos
Heterocromatina/química , Interferon beta/genética , Fator de Transcrição YY1/metabolismo , Animais , Sítios de Ligação , Linhagem Celular , DNA Satélite/análise , Camundongos , Vírus da Doença de Newcastle/fisiologia , Regiões Promotoras Genéticas , Vírus da Febre do Vale do Rift/fisiologia , Ativação Transcricional
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