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Complex multi-enhancer contacts captured by genome architecture mapping

机译：基因组架构图捕获的复杂多增强子接触

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摘要

The organization of the genome in the nucleus and the interactions of genes with their regulatory elements are key features of transcriptional control and their disruption can cause disease. Here we report a genome-wide method, genome architecture mapping (GAM), for measuring chromatin contacts and other features of three-dimensional chromatin topology on the basis of sequencing DNA from a large collection of thin nuclear sections. We apply GAM to mouse embryonic stem cells and identify enrichment for specific interactions between active genes and enhancers across very large genomic distances using a mathematical model termed SLICE (statistical inference of co-segregation). GAM also reveals an abundance of three-way contacts across the genome, especially between regions that are highly transcribed or contain super-enhancers, providing a level of insight into genome architecture that, owing to the technical limitations of current technologies, has previously remained unattainable. Furthermore, GAM highlights a role for gene-expressionspecific contacts in organizing the genome in mammalian nuclei.
机译：基因组在细胞核中的组织以及基因与其调控元件的相互作用是转录控制的关键特征，它们的破坏会导致疾病。在这里，我们报告了一种全基因组方法，即基因组架构图（GAM），用于基于大量薄核切片的DNA测序来测量染色质接触和三维染色质拓扑的其他特征。我们将GAM应用于小鼠胚胎干细胞，并使用称为SLICE的数学模型（共分离的统计推断），在非常大的基因组距离内鉴定出活性基因与增强子之间特定相互作用的富集。 GAM还揭示了整个基因组的大量三向接触，尤其是在高度转录或包含超级增强子的区域之间，从而提供了对基因组架构的深入了解，而由于当前技术的技术局限性，以前无法实现。此外，GAM强调了基因表达特异性接触在组织哺乳动物核基因组中的作用。

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  • 来源
    《Nature》 |2017年第7646期|519-524|共6页
  • 作者

    Beagrie Robert A.; Scialdone Antonio; Schueler Markus; Kraemer Dorothee C. A.; Chotalia Mita; Xie Sheila Q.; Barbieri Mariano; de Santiago Ines; Lavitas Liron-Mark; Branco Miguel R.; Fraser James; Dostie Josee; Game Laurence; Dillon Niall; Edwards Paul A. W.; Nicodemi Mario; Pombo Ana;

  • 作者单位

    Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Epigenet Regulat & Chromatin Architecture Grp, Robert Rossle St, D-13125 Berlin, Germany|Imperial Coll London, MRC London Inst Med Sci, Genome Funct Grp, Hammersmith Hosp Campus, London W12 0NN, England|Imperial Coll London, MRC London Inst Med Sci, Gene Regulat & Chromatin Grp, Hammersmith Hosp Campus, London W12 0NN, England;

    Univ Napoli Fed II INFN Napoli, Complesso Univ Monte, Dipartimento Fis, I-80126 Naples, Italy|Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England;

    Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Epigenet Regulat & Chromatin Architecture Grp, Robert Rossle St, D-13125 Berlin, Germany;

    Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Epigenet Regulat & Chromatin Architecture Grp, Robert Rossle St, D-13125 Berlin, Germany;

    Imperial Coll London, MRC London Inst Med Sci, Genome Funct Grp, Hammersmith Hosp Campus, London W12 0NN, England;

    Imperial Coll London, MRC London Inst Med Sci, Genome Funct Grp, Hammersmith Hosp Campus, London W12 0NN, England|Imperial Coll London, MRC London Inst Med Sci, Single Mol Imaging Grp, Hammersmith Hosp Campus, London W12 0NN, England;

    Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Epigenet Regulat & Chromatin Architecture Grp, Robert Rossle St, D-13125 Berlin, Germany;

    Imperial Coll London, MRC London Inst Med Sci, Genome Funct Grp, Hammersmith Hosp Campus, London W12 0NN, England|Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr,Robinson Way, Cambridge CB2 1TN, England;

    Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Epigenet Regulat & Chromatin Architecture Grp, Robert Rossle St, D-13125 Berlin, Germany|Imperial Coll London, MRC London Inst Med Sci, Genome Funct Grp, Hammersmith Hosp Campus, London W12 0NN, England;

    Imperial Coll London, MRC London Inst Med Sci, Genome Funct Grp, Hammersmith Hosp Campus, London W12 0NN, England|Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England;

    McGill Univ, Goodman Canc Res Ctr, Dept Biochem, Montreal, PQ H3G 1Y6, Canada;

    McGill Univ, Goodman Canc Res Ctr, Dept Biochem, Montreal, PQ H3G 1Y6, Canada;

    Imperial Coll London, MRC London Inst Med Sci, Genom Lab, Hammersmith Hosp Campus, London W12 0NN, England;

    Univ Cambridge, Hutchison MRC Res Ctr, Dept Pathol, Cambridge CB2 0XZ, England;

    Univ Napoli Fed II INFN Napoli, Complesso Univ Monte, Dipartimento Fis, I-80126 Naples, Italy;

    Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Epigenet Regulat & Chromatin Architecture Grp, Robert Rossle St, D-13125 Berlin, Germany|Imperial Coll London, MRC London Inst Med Sci, Genome Funct Grp, Hammersmith Hosp Campus, London W12 0NN, England|BIH, D-10117 Berlin, Germany|Humboldt Univ, Inst Biol, D-10115 Berlin, Germany;

  • 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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