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首页> 外文期刊>Molecular and Cellular Biology >Functional analysis of the individual enhancer core sequences of polyomavirus: cell-specific uncoupling of DNA replication from transcription.
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Functional analysis of the individual enhancer core sequences of polyomavirus: cell-specific uncoupling of DNA replication from transcription.

机译：多瘤病毒的单个增强子核心序列的功能分析：DNA复制与转录的细胞特异性解偶联。

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Polyomavirus (Py) enhancer core elements were compared for their ability to activate Py early transcription and DNA replication in mouse 3T6 cells, lymphoid cell lines, and undifferentiated embryonal carcinoma cells. By examining the pattern of genetic change in a number of cell-specific Py variants, we identified subenhancer sequences that may be functionally important for virus replication. Four such distinct enhancer consensus sequences were synthesized and designated as the A core (homologous with adenovirus 5 E1A enhancer), B core (homologous to the simian virus 40 A enhancer core), C core (containing an inverted repeat within the Py B enhancer), and BPV core (homologous to the bovine papillomavirus enhancer). When used to replace the complete Py B enhancer, single copies of all but the BPV element were able to fully activate Py DNA replication after transfection, but this activation was usually cell type specific. In the PCC4 embryonal carcinoma cells, only the A-core sequence was able to activate transcription and DNA replication. The BPV core sequence containing the Py F441 point change was unable to activate DNA replication in the F9 embryonal carcinoma or any other cell line. No single insertion element was dominant nor did these elements display the wild-type enhancer pattern of cell-specific activation of DNA replication. In addition, differential effects were often observed on the activation of transcription versus DNA replication. In 3T6 cells, transcription could be highly activated by the A core without a corresponding activation of DNA replication. In murine T lymphoid cell lines, the B core activated DNA replication without a corresponding increase in transcription. Furthermore, both DNA replication and, to a lesser degree, transcription often showed a strong tissue-specific dependence on the polarity of the inserted core element for activation.
机译：比较了多瘤病毒（Py）增强子核心元件在小鼠3T6细胞，淋巴样细胞系和未分化的胚胎癌细胞中激活Py早期转录和DNA复制的能力。通过检查许多特定于细胞的Py变体的遗传变化模式，我们确定了可能对病毒复制具有重要功能的亚增强子序列。合成了四个不同的增强子共有序列，分别命名为A核心（与腺病毒5 E1A增强子同源），B核心（与猿猴病毒40 A增强子核心同源），C核心（在Py B增强子内包含反向重复序列）和BPV核心（与牛乳头瘤病毒增强子同源）。当用来替代完整的Py B增强子时，除了BPV元件外，所有其他单拷贝都能在转染后完全激活Py DNA复制，但是这种激活通常是细胞类型特异性的。在PCC4胚胎癌细胞中，只有A核心序列能够激活转录和DNA复制。含有Py F441点变化的BPV核心序列无法激活F9胚胎癌或任何其他细胞系中的DNA复制。没有单个插入元件占主导，这些元件也没有显示DNA复制的细胞特异性激活的野生型增强子模式。此外，经常观察到转录激活与DNA复制之间的差异作用。在3T6细胞中，转录可能被A核高度激活，而没有相应的DNA复制激活。在鼠T淋巴样细胞系中，B核激活了DNA复制而没有相应的转录增加。此外，DNA复制和较小程度的转录通常都显示出强烈的组织特异性依赖于插入的激活核心元件的极性。

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