The win locus involved in activation of the distal N-myc2 gene upon WHV integration in woodchuck liver tumors harbors S/MAR elements
The win locus involved in activation of the distal N-myc2 gene upon WHV integration in woodchuck liver tumors harbors S/MAR elements
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DOI：
10.1016/j.virol.2004.08.008
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发表时间：
2004-11-10
期刊：
影响因子：
3.7
通讯作者：
Rapicetta, M
中科院分区：
文献类型：
--
作者：
Bruni, R;D'Ugo, E;Rapicetta, M
土拨鼠肝炎病毒（WHV）和土拨鼠（旱獭）是B肝炎病毒（HBV）诱导的肝细胞癌（HCC）模型。在土拨鼠肝肿瘤中，N-myc 2原癌基因经常被WHV整合激活，无论是在基因附近还是在b3 n和win下游位点，分别位于N-myc 2的10和150 kb处。一个支架/基质附着区（S/MAR）的调节元件被证明是在b3 n，可能介导激活的上游N-myc 2基因后，WHV整合。为了研究S/MAR元件是否也存在于WHV中，我们克隆了WHV在该位点插入的主要区域的17-kb DNA片段并进行了测序。通过标准的体外结合测定法测试跨越通过序列分析预测的候选S/MAR的重叠亚克隆片段。结果显示胜利中存在两个S/MAR元素。先前描述的WHV插入相对于S/MAR的分布强化了以下假设，即远端WHV插入附近的S/MAR可能参与N-myc 2的远程激活。(C)2004年爱思唯尔公司All rights reserved.
Woodchuck hepatitis virus (WHV) and the woodchuck (Marmota monax) are models for hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV). In woodchuck liver tumors, the N-myc2 proto-oncogene is frequently activated by WHV integration either close to the gene or in the b3n and win downstream loci, located 10 and 150 kb from N-myc2, respectively. A scaffold/matrix attachment region (S/MAR) regulative element was shown to be in b3n, possibly mediating activation of the upstream N-myc2 gene upon WHV integration. To investigate if S/MAR elements are in win too, a 17-kb DNA fragment corresponding to the major region of WHV insertion in this locus was cloned and sequenced. Overlapping subcloned fragments spanning candidate S/MARs predicted by sequence analysis were tested by standard in vitro binding assays. Results showed the presence of two S/MAR elements in win. The distribution of previously described WHV insertions relative to the S/MARs reinforces the hypothesis that S/MARs nearby distal WHV insertions might be involved in long-range activation of N-myc2. (C) 2004 Elsevier Inc. All rights reserved.