Intranuclear disposition of exogenous DNA in vivo: Silencing, methylation and fragmentation
Intranuclear disposition of exogenous DNA in vivo: Silencing, methylation and fragmentation
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DOI：
10.1016/j.febslet.2006.01.017
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发表时间：
2006-02-06
期刊：
影响因子：
3.5
通讯作者：
Kamiya, H
中科院分区：
文献类型：
--
作者：
Ochiai, H;Harashima, H;Kamiya, H
外源DNA的核内处置对于所施用的DNA的治疗效果是非常重要的。通过基于流体动力学的注射将裸DNA酶质粒DNA递送到小鼠肝脏中，并在不同时间点定量核内质粒DNA、荧光素酶及其mRNA的量。还分析了荧光素酶基因启动子的甲基化。来自一个拷贝的外源DNA的表达效率随时间显著降低，并且DNA被甲基化并降解成片段。出乎意料的是，完整质粒DNA的甲基化程度较低，并且不随时间增加。相反，片段化DNA比完整质粒更频繁地甲基化。这些结果表明，CpG甲基化和外源DNA的降解及其“沉默”在细胞核中平行发生。(c)2006年欧洲生物化学学会联合会。Elsevier B.V.出版，保留所有权利。
The intranuclear disposition of exogenous DNA is highly important for the therapeutic effects of the administrated DNA. Naked luciferase-plasmid DNA was delivered into mouse liver by a hydrodynamics-based injection, and the amounts of intranuclear plasmid DNA, luciferase, and its mRNA were quantitated at various time points. Methylation of the promoter of the luciferase gene was also analyzed. Expression efficiency from one copy of the exogenous DNA dramatically decreased over time, and the DNA was methylated and degraded into fragments. Unexpectedly, methylation of the intact plasmid DNA was low and did not increase over time. Rather, the fragmented DNA was methylated more frequently than the intact plasmid. These results suggest that the CpG methylation and the degradation of exogenous DNA, and its 'silencing', occurred in parallel in the nucleus. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.