Multiplex-GAM: genome-wide identification of chromatin contacts yields insights overlooked by Hi-C

被引：17

作者：

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

Thieme, Christoph J. J. ^{[1
]}

Annunziatella, Carlo ^{[4
]}

Baugher, Catherine ^{[5
]}

Zhang, Yingnan ^{[5
]}

Schueler, Markus ^{[1
]}

Kukalev, Alexander ^{[1
]}

Kempfer, Rieke ^{[1
,6
]}

Chiariello, Andrea M. M. ^{[4
]}

Bianco, Simona ^{[1
,4
]}

Li, Yichao ^{[5
]}

Davis, Trenton ^{[5
]}

Scialdone, Antonio ^{[7
,8
,9
]}

Welch, Lonnie R. R. ^{[5
]}

Nicodemi, Mario ^{[1
,4
,10
]}

Pombo, Ana ^{[1
,6
]}

机构：

[1] Berlin Inst Med Syst Biol BIMSB, Max Delbruck Ctr Mol Med Helmholtz Assoc MDC, Epigenet Regulat & Chromatin Architecture Grp, Berlin, Germany

[2] Weatherall Inst Mol Med, Lab Gene Regulat, Oxford, England

[3] Wellcome Ctr Human Genet, Chromatin & Dis Grp, Oxford, England

[4] Univ Napoli Federico II, Complesso Univ Monte Sant Angelo, Dipartimento Fis, INFN Napoli,CNR SPIN, Naples, Italy

[5] Ohio Univ, Sch Elect Engn & Comp Sci, Athens, OH 45701 USA

[6] Humboldt Univ, Berlin, Germany

[7] Helmholtz Zentrum Munchen, Inst Epigenet & Stem Cells, German Res Ctr Environm Hlth, Munich, Germany

[8] Helmholtz Zentrum Munchen, Inst Funct Epigenet, German Res Ctr Environm Hlth, Neuherberg, Germany

[9] Helmholtz Zentrum Munchen, Inst Computat Biol, German Res Ctr Environm Hlth, Neuherberg, Germany

[10] MDC Berlin, Berlin Inst Hlth BIH, Berlin, Germany

来源：

NATURE METHODS | 2023年 / 20卷 / 07期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

RNA-POLYMERASE-II; ORGANIZATION; REVEALS; PRINCIPLES; DYNAMICS;

D O I：

10.1038/s41592-023-01903-1

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Multiplex-genome architecture mapping (multiplex-GAM) enables rapid, unbiased, ligation-free mapping of genome-wide chromatin interactions. Technology for measuring 3D genome topology is increasingly important for studying gene regulation, for genome assembly and for mapping of genome rearrangements. Hi-C and other ligation-based methods have become routine but have specific biases. Here, we develop multiplex-GAM, a faster and more affordable version of genome architecture mapping (GAM), a ligation-free technique that maps chromatin contacts genome-wide. We perform a detailed comparison of multiplex-GAM and Hi-C using mouse embryonic stem cells. When examining the strongest contacts detected by either method, we find that only one-third of these are shared. The strongest contacts specifically found in GAM often involve 'active' regions, including many transcribed genes and super-enhancers, whereas in Hi-C they more often contain 'inactive' regions. Our work shows that active genomic regions are involved in extensive complex contacts that are currently underestimated in ligation-based approaches, and highlights the need for orthogonal advances in genome-wide contact mapping technologies.

引用

页码：1037 / +

页数：30

共 49 条

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