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A map of the cis- regulatory sequences in the mouse genome

机译：小鼠基因组中顺式调控序列的图谱

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摘要

The laboratory mouse is the most widely used mammalian model organism in biomedical research. The 2.6 × 10 bases of the mouse genome possess a high degree of conservation with the human genome, so a thorough annotation of the mouse genome will be of significant value to understanding the function of the human genome. So far, most of the functional sequences in the mouse genome have yet to be found, and the cis-regulatory sequences in particular are still poorly annotated. Comparative genomics has been a powerful tool for the discovery of these sequences, but on its own it cannot resolve their temporal and spatial functions. Recently, ChlP-Seq has been developed to identify cis-regulatory elements in the genomes of several organisms including humans, Drosophila melanogaster and Caenorhabditis elegant. Here we apply the same experimental approach to a diverse set of 19 tissues and cell types in the mouse to produce a map of nearly 300,000 murine cis-regulatory sequences. The annotated sequences add up to 11% of the mouse genome, and include more than 70% of conserved non-coding sequences. We define tissue-specific enhancers and identify potential transcription factors regulating gene expression in each tissue or cell type. Finally, we show that much of the mouse genome is organized into domains of coordinately regulated enhancers and promoters. Our results provide a resource for the annotation of functional elements in the mammalian genome and for the study of mechanisms regulating tissue-specific gene expression.%小鼠基因组中c/s-调控序列的识别落在了其他模型生物的后面。在这项研究中，研究人员通过实验手段确定了来自多种不同小鼠组织和细胞类型的近30万个潜在的c/s-调控序列，它们rn构成一个基因组图。该图显示了小鼠基因组中近11%区域的活性启动子、增强子和CTCF(CCCTC一结合因子)点，显著扩充了对哺乳动物调控序列的注解。
机译：实验鼠是生物医学研究中使用最广泛的哺乳动物模型生物。小鼠基因组的2.6×10个碱基与人类基因组具有高度的保守性，因此，对小鼠基因组的彻底注释对于理解人类基因组的功能将具有重要价值。迄今为止，尚未找到小鼠基因组中的大多数功能序列，尤其是顺式调控序列的注释仍很差。比较基因组学一直是发现这些序列的有力工具，但单靠它本身并不能解决它们的时间和空间功能。最近，已开发出ChlP-Seq来鉴定几种生物体（包括人类，果蝇和优雅的秀丽隐杆线虫）的基因组中的顺式调控元件。在这里，我们将相同的实验方法应用于小鼠中19种组织和细胞类型的多样化集合，以产生将近300,000个小鼠顺式调控序列的图。带注释的序列总计占小鼠基因组的11％，包括超过70％的保守非编码序列。我们定义组织特异性增强子，并确定调节每种组织或细胞类型中基因表达的潜在转录因子。最后，我们证明了大部分小鼠基因组都被组织为协调调节的增强子和启动子的区域。我们的结果为哺乳动物基因组中功能元件的注释和调节组织特异性基因表达的机制研究提供了资源。％小鼠基因组中c / s-序列序列的识别落在了其他模型生物的后面。在这一研究中，研究人员通过实验手段确定了来自多种不同的小鼠组织和细胞类型的近30万个潜在的c / s-序列，它们构成了一个基因组图。该图显示了小鼠基因组中近11％区域的活性启动子，增强子和CTCF（CCCTC一结合因子）点，显着扩展了对微小片段序列的注解。

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  • 来源
    《Nature》 |2012年第7409期|p.116-120A4|共6页
  • 作者

    Yin Shen; Feng Yue; David F. McCleary; Zhen Ye; Lee Edsall; Samantha Kuan; Ulrich Wagner; Jesse Dixon; Leonard Lee; Victor V. Lobanenkov; Bing Ren;

  • 作者单位

    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA;

    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA;

    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA;

    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA;

    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA;

    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA;

    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA;

    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA,Medical Scientist Training Program, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA,Biomedical Sciences Graduate Program, University of California, San Diego School of Medicine, 9500Gilman Drive, La Jolla, California 92093-0653, USA;

    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA;

    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Twinbrook I NIAID Facility, Room 1417, 5640 Fishers Lane, Rockville, Maryland 20852, USA;

    Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA,Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, Moores Cancer Center, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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