Liu R, Baillie J, Sissons J G, Sinclair J H
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, UK.
Nucleic Acids Res. 1994 Jul 11;22(13):2453-9. doi: 10.1093/nar/22.13.2453.
We have previously shown that repression of human cytomegalovirus (HCMV) major immediate early (IE) gene expression in non-permissive human teratocarcinoma (T2) cells is associated with a number of nuclear factors which bind to the imperfect dyad symmetry located in the modulator region upstream of the major IE enhancer as well as to the 21 bp repeat elements within the enhancer. Differentiation of T2 cells with retinoic acid (RA) results in a decrease in binding of some of these nuclear factors to these sites and deletion of these specific binding sites from major IE promoter/reporter constructs results in increased IE promoter activity in normally non-permissive cells. In this study, we demonstrate that the transcription factor YY1, which can negatively regulate the adeno-associated virus P5 promoter, directly binds to both the imperfect dyad symmetry and the 21 bp repeat elements in the HCMV major IE promoter/regulatory region and mediates repression of HCMV IE gene expression. This strongly suggests that YY1 plays an important role in regulating HCMV expression in non-permissive cells.
我们先前已经表明，在非允许性人畸胎瘤（T2）细胞中，人巨细胞病毒（HCMV）主要立即早期（IE）基因表达的抑制与多种核因子相关，这些核因子可结合到位于主要IE增强子上游调节区域的不完全二元对称序列以及增强子内的21 bp重复元件上。用视黄酸（RA）诱导T2细胞分化会导致其中一些核因子与这些位点的结合减少，并且从主要IE启动子/报告基因构建体中删除这些特异性结合位点会导致正常非允许性细胞中IE启动子活性增加。在本研究中，我们证明转录因子YY1可负向调节腺相关病毒P5启动子，它能直接结合到HCMV主要IE启动子/调控区域的不完全二元对称序列和21 bp重复元件上，并介导HCMV IE基因表达的抑制。这强烈表明YY1在调节非允许性细胞中的HCMV表达中起重要作用。
