Ioudinkova Elena, Arcangeletti Maria Cristina, Rynditch Alla, De Conto Flora, Motta Federica, Covan Silvia, Pinardi Federica, Razin Sergey V, Chezzi Carlo
Microbiology Section, Department of Pathology and Laboratory Medicine, University of Parma, Viale Antonio Gramsci, 14, 43100 Parma, Italy.
Gene. 2006 Dec 15;384:120-8. doi: 10.1016/j.gene.2006.07.021. Epub 2006 Jul 31.
Non-differentiated THP-1 cells can be infected by human cytomegalovirus (HCMV) Towne strain, which persists in these cells in a non-active (latent) form without undergoing a productive cycle. The same cells become permissive for HCMV lytic infection after induction of cell differentiation by treatment with 12-O-tetradecanoylphorbol-13-acetate. We used this cellular model to study the possible role of histone modifications in the control of HCMV latency. Using chromatin immunoprecipitation with antibodies against histone H3 acetylated or dimethylated in position K9, we demonstrated that in lytically infected cells the HCMV enhancer was associated with heavy acetylated but not dimethylated H3. In the case of latent infection, the HCMV enhancer was associated with neither acetylated nor dimethylated H3. HCMV genes encoding DNA polymerase (early), pp65 (early-late) and pp150 (late) proteins were associated preferentially with acetylated H3 in lytically infected cells and with dimethylated H3 in latently infected cells. These data strongly suggest that K9 methylation of H3 is involved in HCMV gene repression, while association of the above genes with acetylated histones is likely to be necessary for active transcription. It can be postulated that the same histone modifications are used to mark active and repressed genes in both cellular and viral chromatin.
未分化的THP-1细胞可被人巨细胞病毒（HCMV）Towne株感染，该病毒以非活性（潜伏）形式在这些细胞中持续存在，不经历增殖周期。在用12-O-十四烷酰佛波醇-13-乙酸酯处理诱导细胞分化后，相同的细胞对HCMV裂解感染变得易感。我们使用这种细胞模型来研究组蛋白修饰在控制HCMV潜伏中的可能作用。使用针对在K9位置乙酰化或二甲基化的组蛋白H3的抗体进行染色质免疫沉淀，我们证明在裂解感染的细胞中，HCMV增强子与高度乙酰化而非二甲基化的H3相关。在潜伏感染的情况下，HCMV增强子与乙酰化或二甲基化的H3均无关联。编码DNA聚合酶（早期）、pp65（早晚期）和pp150（晚期）蛋白的HCMV基因在裂解感染的细胞中优先与乙酰化的H3相关，而在潜伏感染的细胞中与二甲基化的H3相关。这些数据强烈表明，H3的K9甲基化参与HCMV基因的抑制，而上述基因与乙酰化组蛋白的关联可能是活跃转录所必需的。可以推测，相同的组蛋白修饰用于标记细胞和病毒染色质中的活跃和受抑制基因。
