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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Epigenetic regulation of genetic integrity is reprogrammed during cloning
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Epigenetic regulation of genetic integrity is reprogrammed during cloning

机译：在克隆过程中对基因完整性的表观遗传调控进行了重新编程

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摘要

Cloning by somatic cell nuclear transfer (SCNT) circumvents processes that normally function during gametogenesis to prepare the gamete genomes to support development of new progeny following fertilization. One such process is enhanced maintenance of genetic integrity in germ cells, such that germ cells typically carry fewer spontaneously acquired mutations than somatic cells in the same individual. Thus, embryos produced from somatic cells by SCNT could directly inherit more mutations than naturally conceived embryos. Alternatively, they could inherit epigenetic programming that predisposes more rapid accumulation of de novo mutations during development. We used' a transgenic mouse system to test these possibilities by producing cloned midgestation mouse fetuses from three different donor somatic cell types carrying significantly different initial frequencies of spontaneous mutations. We found that on an individual locus basis, mutations acquired spontaneously in a population of donor somatic cells are not likely to be propagated to cloned embryos by SCNT. In addition, we found that the rate of accumulation of spontaneous mutations was similar in fetuses produced by either natural conception or cloning, indicating that cloned fetuses do not acquire mutations more rapidly than naturally conceived fetuses. These results represent the first direct demonstration that the process of cloning by SCNT does not lead to an increase in the frequency of point mutations. These results also demonstrate that epigenetic mechanisms normally contribute to the regulation of genetic integrity in a tissue-specific manner, and that these mechanisms are subject to reprogramming during cloning.
机译：通过体细胞核转移（SCNT）进行的克隆绕过了通常在配子发生过程中起作用的过程，以制备配子基因组，以支持受精后新后代的发育。一种这样的过程是增强生殖细胞中遗传完整性的维持，从而与同一个体中的体细胞相比，生殖细胞通常携带较少的自发获得的突变。因此，由SCNT从体细胞产生的胚胎比自然设想的胚胎可以直接继承更多的突变。或者，他们可以继承表观遗传程序设计，这种程序设计在开发过程中更容易积累从头突变。我们使用一种转基因小鼠系统，通过从三种不同的供体体细胞类型中克隆出的中期妊娠小鼠胎儿，这些携带自发突变的初始频率明显不同，来测试这些可能性。我们发现，在单个基因座的基础上，在供体体细胞群体中自发获得的突变不太可能通过SCNT传播到克隆的胚胎。此外，我们发现自然受孕或克隆产生的胎儿中自发突变的积累速率相似，这表明克隆的胎儿获得的突变没有比自然怀孕的胎儿更快。这些结果代表了第一个直接证明，即SCNT的克隆过程不会导致点突变频率的增加。这些结果还表明，表观遗传机制通常以组织特异性方式有助于遗传完整性的调节，并且这些机制在克隆过程中会受到重新编程。

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  • 作者

    Patricia Murphey; Yukiko Yamazaki; C. Alex McMahan; Christi A. Walter; Ryuzo Yanagimachi; John R. McCarrey;

  • 作者单位

    Department of Biology, University of Texas, 1 UTSA Circle, San Antonio, TX 78249;

    Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813;

    Departments of Pathology University of Texas Health Science Center,7703 Floyd Curl Drive, San Antonio, TX 78229;

    Departments of Cellular and Structural Biology, University of Texas Health Science Center,7703 Floyd Curl Drive, San Antonio, TX 78229;

    Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813;

    Department of Biology, University of Texas, 1 UTSA Circle, San Antonio, TX 78249;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    epigenetic reprogramming; mutagenesis;

    机译：表观遗传重编程诱变;

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