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Complex multi-enhancer contacts captured by Genome Architecture Mapping (GAM)

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. We developed a novel genome-wide method, Genome Architecture Mapping (GAM), for measuring chromatin contacts,...

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Detalles Bibliográficos
Autores principales: Beagrie, Robert A., Scialdone, Antonio, Schueler, Markus, Kraemer, Dorothee C.A., Chotalia, Mita, Xie, Sheila Q., Barbieri, Mariano, de Santiago, Inês, Lavitas, Liron-Mark, Branco, Miguel R., Fraser, James, Dostie, Josée, Game, Laurence, Dillon, Niall, Edwards, Paul A.W., Nicodemi, Mario, Pombo, Ana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366070/
https://www.ncbi.nlm.nih.gov/pubmed/28273065
http://dx.doi.org/10.1038/nature21411
Descripción
Sumario: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. We developed a novel genome-wide method, Genome Architecture Mapping (GAM), for measuring chromatin contacts, and other features of three-dimensional chromatin topology, based on sequencing DNA from a large collection of thin nuclear sections. We apply GAM to mouse embryonic stem cells and identify an enrichment for specific interactions between active genes and enhancers across very large genomic distances, using a mathematical model ‘SLICE’ (Statistical Inference of Co-segregation). GAM also reveals an abundance of three-way contacts genome-wide, especially between regions that are highly transcribed or contain super-enhancers, highlighting a previously inaccessible complexity in genome architecture and a major role for gene-expression specific contacts in organizing the genome in mammalian nuclei.