CELL PHENOTYPE-DEPENDENT CONTROL OF EPSTEIN-BARR-VIRUS LATENT MEMBRANE PROTEIN-1 GENE REGULATORY SEQUENCES
CELL PHENOTYPE-DEPENDENT CONTROL OF EPSTEIN-BARR-VIRUS LATENT MEMBRANE PROTEIN-1 GENE REGULATORY SEQUENCES
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DOI：
10.1006/viro.1993.1347
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发表时间：
1993-07-01
期刊：
影响因子：
3.7
通讯作者：
RYMO, L
中科院分区：
文献类型：
--
作者：
FAHRAEUS, R;JANSSON, A;RYMO, L
生长转化相关EB病毒编码基因的差异调节取决于宿主细胞表型。我们先前已经鉴定了LMP 1基因的LMP 1调节区（LRS）5′（+40至-634），并分析了其在EBV阴性伯基特淋巴瘤系DG 75中转录起始的作用（Fåhraeuset al.，1990年a）。为了研究LMP 1基因调控的细胞表型依赖性，我们现在比较了在存在和不存在病毒编码的核抗原EBNA 2的情况下，B淋巴细胞和上皮细胞来源的细胞系中的阳性和阴性作用LRS元件的活性。我们的结果表明，仅含有LRS的-54/+40区域的报告质粒在所有测试的细胞系中是有活性的。此外，发现先前鉴定的-144/-54区域中的负性顺式元件抑制启动子活性，而与细胞表型无关。EBNA 2能够覆盖所有B细胞来源的细胞系中的负性元件的作用，而它在上皮细胞系中没有作用。EBNA 2的正效应是由-214/-144-bp区域的顺式作用元件介导的。在所有6个测试的上皮来源的细胞系中，携带全长LRS的报告质粒是有活性的，不依赖于EBNA 2。这些构建体中的LMP 1启动子通过在-214/-144和-324/-214位置的EBNA 2非依赖性阳性元件的协同作用而被激活，所述EBNA 2非依赖性阳性元件抵消了阴性LRS元件的作用。
Growth transformation-associated Epstein-Barr virus-encoded genes are differentially regulated depending on the host cell phenotype. We have previously identified an LMP1 regulatory region (LRS) 5′ of the LMP1 gene (+40 to -634) and analyzed its role in transcription initiation in the EBV-negative Burkitt's lymphoma line DG 75 (Fåhraeuset al.,1990a). In order to investigate the cell phenotype dependence of LMP1 gene regulation we have now compared the activity of positive and negativecis-acting LRS elements in cell lines of B lymphoid and epithelial cell origin in the presence and absence of the virus-encoded nuclear antigen EBNA2. Our results show that reporter plasmids that contain only the -54/+40 region of LRS are active in all tested cell lines. Furthermore, the previously identified negativecis-elements in the -144/-54 region were found to suppress promoter activity independent of the cell phenotype. EBNA2 was able to override the effect of the negative elements in all lines of B-cell origin, whereas it had no effect in epithelial lines. The positive effect of EBNA2 was mediated by cis-acting elements in the -214/-144-bp region. In all six tested cell lines of epithelial origin, reporter plasmids that carried the full-length LRS were active, independent of EBNA2. The LMP1 promoter in these constructs was activated by the concerted action of EBNA2-independent, positive elements in the -214/-144 and -324/-214 positions that counteracted the effect of the negative LRS elements.