Complex multi-enhancer contacts captured by genome architecture mapping

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 Fraser, Josée Dostie, Laurence Game, Niall Dillon, Paul A. W. Edwards, Mario Nicodemi () and Ana Pombo ()
Additional contact information
Robert A. Beagrie: Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Robert-Rössle Straße
Antonio Scialdone: Università di Napoli Federico II, and INFN Napoli, Complesso Universitario di Monte Sant’Angelo
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
Mariano Barbieri: Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Robert-Rössle Straße
Inês de Santiago: Genome Function Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus
Liron-Mark Lavitas: Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Robert-Rössle Straße
Miguel R. Branco: Genome Function Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus
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

Nature, 2017, vol. 543, issue 7646, 519-524

Abstract: 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.

Date: 2017
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DOI: 10.1038/nature21411

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