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|a dc
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|a Schwarzer, Wibke
|e author
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|a Massachusetts Institute of Technology. Department of Physics
|e contributor
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|a Massachusetts Institute of Technology. Institute for Medical Engineering & Science
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|a Abdennur, Nezar
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|a Goloborodko, Anton
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|a Pekowska, Aleksandra
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|a Fudenberg, Geoffrey
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|a Loe-Mie, Yann
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|a Fonseca, Nuno A
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|a Huber, Wolfgang
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|a Haering, Christian H.
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|a Mirny, Leonid A
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|a Spitz, Francois
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|a Two independent modes of chromatin organization revealed by cohesin removal
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|b Springer Science and Business Media,
|c 2020-08-05T19:03:33Z.
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|z Get fulltext
|u https://hdl.handle.net/1721.1/126477
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|a 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.
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|a National Institutes of Health (Grant R01-GM114190, U54-DK107980)
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|a National Science Foundation (Grant 1504942)
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|a en
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|a Article
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|t Nature
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