Two independent modes of chromatin organization revealed by cohesin removal
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 fo...
| Main Authors: | , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Springer Science and Business Media
2020
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| Online Access: | https://hdl.handle.net/1721.1/126477 |
| _version_ | 1826198302033444864 |
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| author | Schwarzer, Wibke Abdennur, Nezar Goloborodko, Anton Pekowska, Aleksandra Fudenberg, Geoffrey Loe-Mie, Yann Fonseca, Nuno A Huber, Wolfgang Haering, Christian H. Mirny, Leonid A Spitz, Francois |
| author2 | Massachusetts Institute of Technology. Department of Physics |
| author_facet | Massachusetts Institute of Technology. Department of Physics Schwarzer, Wibke Abdennur, Nezar Goloborodko, Anton Pekowska, Aleksandra Fudenberg, Geoffrey Loe-Mie, Yann Fonseca, Nuno A Huber, Wolfgang Haering, Christian H. Mirny, Leonid A Spitz, Francois |
| author_sort | Schwarzer, Wibke |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:02:44Z |
| format | Article |
| id | mit-1721.1/126477 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:02:44Z |
| publishDate | 2020 |
| publisher | Springer Science and Business Media |
| record_format | dspace |
| spelling | mit-1721.1/1264772022-09-27T16:43:09Z Two independent modes of chromatin organization revealed by cohesin removal Schwarzer, Wibke Abdennur, Nezar Goloborodko, Anton Pekowska, Aleksandra Fudenberg, Geoffrey Loe-Mie, Yann Fonseca, Nuno A Huber, Wolfgang Haering, Christian H. Mirny, Leonid A Spitz, Francois Massachusetts Institute of Technology. Department of Physics Massachusetts Institute of Technology. Institute for Medical Engineering & Science 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. National Institutes of Health (Grant R01-GM114190, U54-DK107980) National Science Foundation (Grant 1504942) 2020-08-05T19:03:33Z 2020-08-05T19:03:33Z 2017-09 2016-12 2019-10-09T16:13:04Z Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 https://hdl.handle.net/1721.1/126477 Wibke Schwarzer, et al. "Two independent modes of chromatin organization revealed by cohesin removal." Nature 551, 7678 (September 2017): 51–56 © 2017 Macmillan Publishers Limited, part of Springer Nature en http://dx.doi.org/10.1038/nature24281 Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Springer Science and Business Media PMC |
| spellingShingle | Schwarzer, Wibke Abdennur, Nezar Goloborodko, Anton Pekowska, Aleksandra Fudenberg, Geoffrey Loe-Mie, Yann Fonseca, Nuno A Huber, Wolfgang Haering, Christian H. Mirny, Leonid A Spitz, Francois Two independent modes of chromatin organization revealed by cohesin removal |
| title | Two independent modes of chromatin organization revealed by cohesin removal |
| title_full | Two independent modes of chromatin organization revealed by cohesin removal |
| title_fullStr | Two independent modes of chromatin organization revealed by cohesin removal |
| title_full_unstemmed | Two independent modes of chromatin organization revealed by cohesin removal |
| title_short | Two independent modes of chromatin organization revealed by cohesin removal |
| title_sort | two independent modes of chromatin organization revealed by cohesin removal |
| url | https://hdl.handle.net/1721.1/126477 |
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