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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Long-range enhancers on 8q24 regulate c-Myc
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Long-range enhancers on 8q24 regulate c-Myc

机译：8q24上的远程增强子调节c-Myc

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摘要

Recent genomewide association studies have found multiple genetic variants on chromosome 8q24 that are significantly associated with an increased susceptibility to prostate, colorectal, and breast cancer. These risk loci are located in a "gene desert," a few hundred kilobases telomeric to the Myc gene. To date, the biological mechanism(s) underlying these associations remain unclear. It has been speculated that these 8q24 genetic variant(s) might affect Myc expression by altering its regulation or amplification status. Here, we show that multiple enhancer elements are present within this region and that they can regulate transcription of Myc. We also demonstrate that one such enhancer element physically interacts with the Myc promoter via transcription factor Tcf-4 binding and acts in an allele specific manner to regulate Myc expression.
机译：最近的全基因组关联研究发现，染色体8q24上存在多个遗传变异，这些变异与对前列腺癌，结肠直肠癌和乳腺癌的敏感性增加显着相关。这些危险基因座位于“基因沙漠”中，与Myc基因端粒数百个碱基。迄今为止，这些关联的生物学机制仍不清楚。已经推测这些8q24遗传变异体可能通过改变其调控或扩增状态而影响Myc表达。在这里，我们表明该区域内存在多个增强子元件，它们可以调节Myc的转录。我们还证明了一种这样的增强子元件通过转录因子Tcf-4结合与Myc启动子发生物理相互作用，并以等位基因特异性方式起作用，以调节Myc表达。

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  • 作者

    Jose Sotelo; Dominic Esposito; Maria Ana Duhagon; Kelley Banfield; Jennifer Mehalko; Hongling Liao; Robert M. Stephens; Timothy J. R. Harris; David J. Munroe; Xiaolin Wu;

  • 作者单位

    Laboratory of Molecular Technology, National Cancer Institute-Frederick, Frederick, MD, 21702, USA Advanced Technology Program, National Cancer Institute-Frederick, Frederick, MD, 21702, USA;

    rnAdvanced Technology Program, National Cancer Institute-Frederick, Frederick, MD, 21702, USA Protein Expression Laboratory, National Cancer Institute-Frederick, Frederick, MD, 21702, USA;

    rnCancer Stem Cell Section, Laboratory of Cancer Prevention, National Cancer Institute-Frederick, Frederick, MD, 21702, USA;

    rnLaboratory of Molecular Technology, National Cancer Institute-Frederick, Frederick, MD, 21702, USA Advanced Technology Program, National Cancer Institute-Frederick, Frederick, MD, 21702, USA;

    rnAdvanced Technology Program, National Cancer Institute-Frederick, Frederick, MD, 21702, USA Protein Expression Laboratory, National Cancer Institute-Frederick, Frederick, MD, 21702, USA;

    rnLaboratory of Molecular Technology, National Cancer Institute-Frederick, Frederick, MD, 21702, USA Advanced Technology Program, National Cancer Institute-Frederick, Frederick, MD, 21702, USA;

    rnAdvanced Technology Program, National Cancer Institute-Frederick, Frederick, MD, 21702, USA Advanced Biomedical Computing Center, SAIC-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD 21702 USA;

    rnAdvanced Technology Program, National Cancer Institute-Frederick, Frederick, MD, 21702, USA;

    rnAdvanced Technology Program, National Cancer Institute-Frederick, Frederick, MD, 21702, USA;

    rnLaboratory of Molecular Technology, National Cancer Institute-Frederick, Frederick, MD, 21702, USA Advanced Technology Program, National Cancer Institute-Frederick, Frederick, MD, 21702, USA;

  • 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);
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