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Complex multi-enhancer contacts captured by genome architecture mapping

Author

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  • Robert A. Beagrie

    (Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Robert-Rössle Straße
    Genome Function Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus
    Gene Regulation and Chromatin Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus)

  • Antonio Scialdone

    (Università di Napoli Federico II, and INFN Napoli, Complesso Universitario di Monte Sant’Angelo
    †Present addresses: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK (A.S.); Single Molecule Imaging Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK (S.Q.X.); Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK (I.d.S.); Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK (M.R.B.).)

  • Markus Schueler

    (Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Robert-Rössle Straße)

  • Dorothee C. A. Kraemer

    (Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Robert-Rössle Straße)

  • Mita Chotalia

    (Genome Function Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus)

  • Sheila Q. Xie

    (Genome Function Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus
    †Present addresses: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK (A.S.); Single Molecule Imaging Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK (S.Q.X.); Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK (I.d.S.); Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK (M.R.B.).)

  • Mariano Barbieri

    (Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Robert-Rössle Straße
    Berlin Institute of Health (BIH))

  • Inês de Santiago

    (Genome Function Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus
    †Present addresses: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK (A.S.); Single Molecule Imaging Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK (S.Q.X.); Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK (I.d.S.); Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK (M.R.B.).)

  • Liron-Mark Lavitas

    (Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Robert-Rössle Straße
    Genome Function Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus)

  • Miguel R. Branco

    (Genome Function Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus
    †Present addresses: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK (A.S.); Single Molecule Imaging Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK (S.Q.X.); Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK (I.d.S.); Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK (M.R.B.).)

  • James Fraser

    (McGill University)

  • Josée Dostie

    (McGill University)

  • Laurence Game

    (Genomics Laboratory, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus)

  • Niall Dillon

    (Gene Regulation and Chromatin Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus)

  • Paul A. W. Edwards

    (University of Cambridge)

  • Mario Nicodemi

    (Università di Napoli Federico II, and INFN Napoli, Complesso Universitario di Monte Sant’Angelo)

  • Ana Pombo

    (Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Robert-Rössle Straße
    Genome Function Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus
    Berlin Institute of Health (BIH)
    Institute for Biology, Humboldt-Universität zu Berlin)

Abstract

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-expression-specific contacts in organizing the genome in mammalian nuclei.

Suggested Citation

  • Robert A. Beagrie & Antonio Scialdone & Markus Schueler & Dorothee C. A. Kraemer & Mita Chotalia & Sheila Q. Xie & Mariano Barbieri & Inês de Santiago & Liron-Mark Lavitas & Miguel R. Branco & James F, 2017. "Complex multi-enhancer contacts captured by genome architecture mapping," Nature, Nature, vol. 543(7646), pages 519-524, March.
    • Handle: RePEc:nat:nature:v:543:y:2017:i:7646:d:10.1038_nature21411
    DOI: 10.1038/nature21411
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    Citations

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    Cited by:

    1. Zhen Wah Tan & Enrico Guarnera & Igor N Berezovsky, 2018. "Exploring chromatin hierarchical organization via Markov State Modelling," PLOS Computational Biology, Public Library of Science, vol. 14(12), pages 1-35, December.
    2. Guang Shi & D. Thirumalai, 2023. "A maximum-entropy model to predict 3D structural ensembles of chromatin from pairwise distances with applications to interphase chromosomes and structural variants," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Milad Mokhtaridoost & Jordan J. Chalmers & Marzieh Soleimanpoor & Brandon J. McMurray & Daniella F. Lato & Son C. Nguyen & Viktoria Musienko & Joshua O. Nash & Sergio Espeso-Gil & Sameen Ahmed & Kate , 2024. "Inter-chromosomal contacts demarcate genome topology along a spatial gradient," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Gabrielle A. Dotson & Can Chen & Stephen Lindsly & Anthony Cicalo & Sam Dilworth & Charles Ryan & Sivakumar Jeyarajan & Walter Meixner & Cooper Stansbury & Joshua Pickard & Nicholas Beckloff & Amit Su, 2022. "Deciphering multi-way interactions in the human genome," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Hao Wang & Jiaxin Yang & Yu Zhang & Jianliang Qian & Jianrong Wang, 2022. "Reconstruct high-resolution 3D genome structures for diverse cell-types using FLAMINGO," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    6. Daniela Michelatti & Sven Beyes & Chiara Bernardis & Maria Luce Negri & Leonardo Morelli & Naiara Garcia Bediaga & Vittoria Poli & Luca Fagnocchi & Sara Lago & Sarah D’Annunzio & Nicole Cona & Ilaria , 2024. "Oncogenic enhancers prime quiescent metastatic cells to escape NK immune surveillance by eliciting transcriptional memory," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    7. Nimrod Rappoport & Elad Chomsky & Takashi Nagano & Charlie Seibert & Yaniv Lubling & Yael Baran & Aviezer Lifshitz & Wing Leung & Zohar Mukamel & Ron Shamir & Peter Fraser & Amos Tanay, 2023. "Single cell Hi-C identifies plastic chromosome conformations underlying the gastrulation enhancer landscape," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. Sarah B. Reiff & Andrew J. Schroeder & Koray Kırlı & Andrea Cosolo & Clara Bakker & Luisa Mercado & Soohyun Lee & Alexander D. Veit & Alexander K. Balashov & Carl Vitzthum & William Ronchetti & Kent M, 2022. "The 4D Nucleome Data Portal as a resource for searching and visualizing curated nucleomics data," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    9. Alexandra D’Oto & Jie Fang & Hongjian Jin & Beisi Xu & Shivendra Singh & Anoushka Mullasseril & Victoria Jones & Ahmed Abu-Zaid & Xinyu Buttlar & Bailey Cooke & Dongli Hu & Jason Shohet & Andrew J. Mu, 2021. "KDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN-amplified neuroblastoma," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    10. Mattia Conte & Ehsan Irani & Andrea M. Chiariello & Alex Abraham & Simona Bianco & Andrea Esposito & Mario Nicodemi, 2022. "Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    11. Jia-Yong Zhong & Longjian Niu & Zhuo-Bin Lin & Xin Bai & Ying Chen & Feng Luo & Chunhui Hou & Chuan-Le Xiao, 2023. "High-throughput Pore-C reveals the single-allele topology and cell type-specificity of 3D genome folding," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    12. Claire Marchal & Nivedita Singh & Zachary Batz & Jayshree Advani & Catherine Jaeger & Ximena Corso-Díaz & Anand Swaroop, 2022. "High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    13. Annkatrin Bressin & Olga Jasnovidova & Mirjam Arnold & Elisabeth Altendorfer & Filip Trajkovski & Thomas A. Kratz & Joanna E. Handzlik & Denes Hnisz & Andreas Mayer, 2023. "High-sensitive nascent transcript sequencing reveals BRD4-specific control of widespread enhancer and target gene transcription," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    14. Abhijit Chakraborty & Jeffrey G. Wang & Ferhat Ay, 2022. "dcHiC detects differential compartments across multiple Hi-C datasets," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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