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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Replication allows inactivation of a knocked-in locus control region in inappropriate cell lineages
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Replication allows inactivation of a knocked-in locus control region in inappropriate cell lineages

机译：复制使失活的细胞谱系中敲入的基因座控制区失活

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摘要

To study the influence of a locus control region (LCR) on the expression of a highly characterized, developmentally regulated locus, we have targeted the hCD2-LCR as a single copy into the endogenous mouse CD8 gene complex. Two knock-in mouse lines that differ in the integration site of the hCD2-LCR within the mCD8 gene complex were generated, and the influence on expression of the CD8 coreceptor was assessed. In these mice the normal developmental silencing of the CD8 genes in the CD4 lineage is deregulated, and the mice develop CD4~+ cells that also express the CD8 genes. This is accompanied by the physical maintenance of the CD8 genes within an extended loop away from their subchromoso-mal territory. Further analysis of these mice revealed unexpected fluid chromatin dynamics, whereby the LCR can be initially dominant over the endogenous CD8 gene-repressive regulatory processes present in CD4~+ cells but is continuously contested by them, resulting in the eventual inactivation of the inserted LCR, probably as a result of multiple rounds of replication.
机译：为了研究基因座控制区（LCR）对高度表征的，发育受调控的基因座表达的影响，我们将hCD2-LCR作为单拷贝靶向内源小鼠CD8基因复合体。产生了两种在mCD8基因复合物中hCD2-LCR整合位点不同的敲入小鼠系，并评估了对CD8共受体的表达的影响。在这些小鼠中，CD4谱系中CD8基因的正常发育沉默被解除，并且小鼠发育出也表达CD8基因的CD4 +细胞。这伴随着CD8基因在远离其染色体下区域的扩展环中的物理维持。对这些小鼠的进一步分析揭示了意料之外的流体染色质动力学，因此LCR最初可能会优先于CD4〜+细胞中存在的内源性CD8基因阻遏性调节过程，但不断被它们竞争，导致插入的LCR最终失活，可能是多轮复制的结果。

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  • 作者

    Ursula Menzel; Eleni Ktistaki; Mauro Tolaini; Henrique Veiga-Fernandes; Dimitris Kioussis;

  • 作者单位

    Division of Molecular Immunology, National Institute for Medical Research, Medical Research Council, London NW7 1AA, United Kingdom;

    rnDivision of Molecular Immunology, National Institute for Medical Research, Medical Research Council, London NW7 1AA, United Kingdom;

    rnDivision of Molecular Immunology, National Institute for Medical Research, Medical Research Council, London NW7 1AA, United Kingdom;

    rnDivision of Molecular Immunology, National Institute for Medical Research, Medical Research Council, London NW7 1AA, United Kingdom;

    rnDivision of Molecular Immunology, National Institute for Medical Research, Medical Research Council, London NW7 1AA, United Kingdom;

  • 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
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  • 关键词

    CD8 locus; hCD2 locus control region; knock-in; lymphocyte development; chromatin structure;

    机译：CD8基因座;hCD2基因座控制区;敲入淋巴细胞发育;染色质结构;

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