Two independent modes of chromatin organization revealed by cohesin removal

Autor: Anton Goloborodko, Geoffrey Fudenberg, Nuno A. Fonseca, Nezar Abdennur, Christian H. Haering, François Spitz, Aleksandra Pekowska, Yann Loe-Mie, Leonid A. Mirny, Wolfgang Huber, Wibke Schwarzer
Přispěvatelé: European Molecular Biology Laboratory [Heidelberg] (EMBL), Massachusetts Institute of Technology (MIT), Génomique et Epigénomique du Développement des Vertébrés - Genomics and Epigenomics of Vertebrates Development, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Department of Physics [MIT Cambridge], W.S. and A.P. were supported by an EMBL Interdisciplinary Postdoc (EIPOD) Fellowship under Marie Curie Actions COFUND. The work in the Mirny laboratory is supported by R01 GM114190, U54 DK107980 from the NIH, and 1504942 from the NSF. The collaboration is also partially supported by the MIT-France MISTI Fund. The work in the Spitz laboratory was supported by EMBL, the Pasteur Institute and the Deutsche Forschungsgesellschaft (DFG grant: SP 1331/3-1) and included funding from the European Commission’s Seventh Framework Programme through the Collaborative Research Project RADIANT (grant agreement no. 305626, to W.H.)., European Project: 305626,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,RADIANT(2012), Génomique et Epigénomique du Développement des Vertébrés - Genomics and Epigenomics of Vertebrate Development, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Nature
Nature, 2017, 551 (7678), pp.51-56. ⟨10.1038/nature24281⟩
Nature, Nature Publishing Group, 2017, 551 (7678), pp.51-56. ⟨10.1038/nature24281⟩
ISSN: 0028-0836
1476-4687
1476-4679
DOI: 10.1038/nature24281⟩
Popis: International audience; Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes. By contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the three-dimensional organization of the genome results from the interplay of two independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; and cohesin-dependent formation of TADs, possibly by loop extrusion, which helps to guide distant enhancers to their target genes.
Databáze: OpenAIRE
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