Régulation de la Transcription et Maladies Génétiques, CNRS FRE3235, Université Paris Descartes, 45 rue des Saints Pères, 75270, Paris cedex 06, France.
Nucleic Acids Res. 2012 May;40(10):4396-411. doi: 10.1093/nar/gks050. Epub 2012 Jan 28.
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.
核架构以及基因核定位可以调节基因表达。在这项工作中，我们分析了干扰素-β（IFN-β）基因座的核位置，该基因座负责建立先天抗病毒反应，同时分析了其与着丝粒周围异染色质（PCH）的关系，与病毒诱导的 IFN-β 基因表达相关联。实验在两种不同的细胞类型中进行，一种是非感染（NI）细胞，另一种是在三种不同病毒感染的时间过程中进行。在 NI 细胞中，我们发现 IFN-β 启动子与 PCH 呈单等位基因关联，这种关联在病毒感染后强烈减少。IFN-β 基因座与这些抑制区域的分离先于强烈的启动子转录激活，并且在感染后 12 小时内是可逆的。在用一种异常使 IFN-β 基因处于抑制状态的病毒感染后，未观察到分离。病毒感染后诱导的分离专门针对 IFN-β 基因座，而不影响 PCH 簇的一般结构和核分布。使用稳定转染野生型或突变 IFN-β 启动子的细胞系，我们确定了 IFN-β 启动子的近端区域，该区域包含 YY1 DNA 结合位点，该区域在病毒感染前后调节 IFN-β 启动子与 PCH 的结合。
