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Complex multi-enhancer contacts captured by genome architecture mapping

Official URL:https://doi.org/10.1038/nature21411
PubMed:View item in PubMed
Creators Name:Beagrie, R.A. and Scialdone, A. and Schueler, M. and Kraemer, D.C.A. and Chotalia, M. and Xie, S.Q. and Barbieri, M. and de Santiago, I. and Lavitas, L.M. and Branco, M.R. and Fraser, J. and Dostie, J. and Game, L. and Dillon, N. and Edwards, P.A.W. and Nicodemi, M. and Pombo, A.
Journal Title:Nature
Journal Abbreviation:Nature
Volume:543
Number:7646
Page Range:519-524
Date:23 March 2017
Keywords:Chromatin, Chromosome Mapping, DNA Sequence Analysis, Genetic Enhancer Elements, Genetic Epigenesis, Genetic Models, Genetic Transcription, Genome, Mouse Embryonic Stem Cells, Animals, Mice
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.
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Item Type:Article

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