Complex multi-enhancer contacts captured by genome architecture mapping.
Complex multi-enhancer contacts captured by genome architecture mapping.
复制标题
DOI：
10.1038/nature21411
复制
发表时间：
2017-03-23
期刊：
影响因子：
64.8
通讯作者：
Pombo A
中科院分区：
文献类型：
--
作者：
Beagrie RA;Scialdone A;Schueler M;Kraemer DC;Chotalia M;Xie SQ;Barbieri M;de Santiago I;Lavitas LM;Branco MR;Fraser J;Dostie J;Game L;Dillon N;Edwards PA;Nicodemi M;Pombo A
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，它们的破坏可能导致疾病。我们开发了一种新的全基因组方法，基因组结构映射（GAM），用于测量染色质接触，和其他功能的三维染色质拓扑结构，基于从大量收集的薄核切片的DNA测序。我们将GAM应用于小鼠胚胎干细胞，并使用数学模型“SLICE”（共分离的统计推断）确定活性基因和增强子之间跨非常大的基因组距离的特定相互作用的富集。GAM还揭示了丰富的三向接触全基因组，特别是在高度转录或含有超级增强子的区域之间，突出了基因组结构中以前难以接近的复杂性和基因表达特异性接触在组织哺乳动物细胞核中的基因组中的重要作用。
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. We developed a novel genome-wide method, Genome Architecture Mapping (GAM), for measuring chromatin contacts, and other features of three-dimensional chromatin topology, based on sequencing DNA from a large collection of thin nuclear sections. We apply GAM to mouse embryonic stem cells and identify an enrichment for specific interactions between active genes and enhancers across very large genomic distances, using a mathematical model ‘SLICE’ (Statistical Inference of Co-segregation). GAM also reveals an abundance of three-way contacts genome-wide, especially between regions that are highly transcribed or contain super-enhancers, highlighting a previously inaccessible complexity in genome architecture and a major role for gene-expression specific contacts in organizing the genome in mammalian nuclei.