Down-regulation of the major histocompatibility complex class I enhancer in adenovirus type 12-transformed cells is accompanied by an increase in factor binding.
Down-regulation of the major histocompatibility complex class I enhancer in adenovirus type 12-transformed cells is accompanied by an increase in factor binding.
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12 型腺病毒转化细胞中主要组织相容性复合物 I 类增强子的下调伴随着因子结合的增加。
DOI：
10.1128/jvi.66.12.6969-6978.1992
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发表时间：
1992
影响因子：
5.4
通讯作者：
Ricciardi,RP
中科院分区：
文献类型：
--
作者：
Ge,R;Kralli,A;Weinmann,R;Ricciardi,RP
在转化细胞中，腺病毒12型（Ad 12）的E1 A基因抑制主要组织相容性复合体I类基因的转录。Ad 12转化细胞的致瘤潜力与这种减少的I类表达相关。相反，E1 A基因的非致瘤性的Ad 5不影响I类表达。我们在此显示，由H-2K启动子（~ 1049 bp）驱动的转染的报告氯霉素乙酰转移酶质粒在Ad 12-中的表达水平比在Ad 5-转化的小鼠细胞中低得多。突变体结构的分析表明，只有83 bp的H-2 DNA，由增强子并列的基础启动子，是足够的这种差异表达。而单独的H-2基础启动子在Ad 12转化的细胞中活性稍低，H-2 TATA盒本身似乎并不重要。H-2增强子被证明是Ad 12 E1 A介导的抑制中的主要元件，因为（i）用猿猴病毒40增强子取代H-2增强子克服了抑制，并且（ii）当与其天然或异源基础启动子并置时，H-2增强子在Ad 5转化细胞中而不是在Ad 12转化细胞中起作用。迁移率变动分析表明，有一个DNA结合活性的5'位点（R2元件）的增强子，是显着高于在Ad 12-比Ad 5转化细胞。这些结果表明，在Ad 12转化的细胞中，I类增强子活性降低，可能至少部分是由于增强子特异性因子的水平较高，可能充当阻遏物。
In transformed cells, the E1A gene of adenovirus type 12 (Ad12) represses transcription of class I genes of the major histocompatibility complex. The tumorigenic potential of Ad12-transformed cells correlates with this diminished class I expression. In contrast, the E1A gene of the nontumorigenic Ad5 does not affect class I expression. We show here that a transfected reporter chloramphenicol acetyltransferase plasmid driven by an H-2K promoter (-1049 bp) was expressed at much lower levels in Ad12- than in Ad5-transformed mouse cells. Analysis of mutant constructs revealed that only 83 bp of H-2 DNA, consisting of the enhancer juxtaposed to the basal promoter, was sufficient for this differential expression. Whereas the H-2 basal promoter alone was somewhat less active in Ad12-transformed cells, the H-2 TATA box itself did not appear to be important. The H-2 enhancer proved to be the principal element in Ad12 E1A-mediated repression, since (i) substitution of the H-2 enhancer by simian virus 40 enhancers overcame the repression, and (ii) when juxtaposed to either its native or heterologous basal promoters, the H-2 enhancer was functional in Ad5- but not Ad12-transformed cells. Mobility shift assays showed that there is a DNA-binding activity to the 5' site (R2 element) of the enhancer that is significantly higher in Ad12- than in Ad5-transformed cells. These results suggest that decreased class I enhancer activity in Ad12-transformed cells may, at least in part, be due to the higher levels of an enhancer-specific factor, possibly acting as a repressor.