Complex multi-enhancer contacts captured by genome architecture mapping

被引：513

作者：

Beagrie, Robert A. ^{[1
,2
,3
]}

Scialdone, Antonio ^{[4
,10
]}

Schueler, Markus ^{[1
]}

Kraemer, Dorothee C. A. ^{[1
]}

Chotalia, Mita ^{[2
]}

Xie, Sheila Q. ^{[2
,11
]}

Barbieri, Mariano ^{[1
]}

de Santiago, Ines ^{[2
,12
]}

Lavitas, Liron-Mark ^{[1
,2
]}

Branco, Miguel R. ^{[2
,13
]}

Fraser, James ^{[6
]}

Dostie, Josee ^{[6
]}

Game, Laurence ^{[7
]}

Dillon, Niall

Edwards, Paul A. W. ^{[8
]}

Nicodemi, Mario ^{[4
]}

Pombo, Ana ^{[1
,2
,5
,9
]}

机构：

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

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

[3] Imperial Coll London, MRC London Inst Med Sci, Gene Regulat & Chromatin Grp, Hammersmith Hosp Campus, London W12 0NN, England

[4] Univ Napoli Fed II INFN Napoli, Complesso Univ Monte, Dipartimento Fis, I-80126 Naples, Italy

[5] BIH, D-10117 Berlin, Germany

[6] McGill Univ, Goodman Canc Res Ctr, Dept Biochem, Montreal, PQ H3G 1Y6, Canada

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

[8] Univ Cambridge, Hutchison MRC Res Ctr, Dept Pathol, Cambridge CB2 0XZ, England

[9] Humboldt Univ, Inst Biol, D-10115 Berlin, Germany

[10] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England

[11] Imperial Coll London, MRC London Inst Med Sci, Single Mol Imaging Grp, Hammersmith Hosp Campus, London W12 0NN, England

[12] Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr,Robinson Way, Cambridge CB2 1TN, England

[13] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England

来源：

NATURE | 2017年 / 543卷 / 7646期

基金：

加拿大健康研究院; 英国医学研究理事会;

关键词：

RNA-POLYMERASE-II; CHROMOSOME CONFORMATION CAPTURE; EMBRYONIC STEM-CELLS; HI-C DATA; ORGANIZATION; TRANSCRIPTION; GENES; REVEALS; DOMAINS; PRINCIPLES;

D O I：

10.1038/nature21411

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

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.

引用

页码：519 / +

页数：25

共 63 条

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Neural Differentiation of Embryonic Stem Cells In Vitro: A Road Map to Neurogenesis in the Embryo [J].