Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture
During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi c...
| Main Authors: | , , , , , , , , , , , , , |
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| פורמט: | Article |
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Proceedings of the National Academy of Sciences
2018
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| גישה מקוונת: | http://hdl.handle.net/1721.1/114761 |
| _version_ | 1826201179755905024 |
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| author | Darrow, Emily M. Huntley, Miriam H. Dudchenko, Olga Stamenova, Elena K. Durand, Neva C. Sun, Zhuo Huang, Su-Chen Sanborn, Adrian L. Machol, Ido Shamim, Muhammad Seberg, Andrew P. Chadwick, Brian P. Aiden, Erez Lieberman Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Darrow, Emily M. Huntley, Miriam H. Dudchenko, Olga Stamenova, Elena K. Durand, Neva C. Sun, Zhuo Huang, Su-Chen Sanborn, Adrian L. Machol, Ido Shamim, Muhammad Seberg, Andrew P. Chadwick, Brian P. Aiden, Erez Lieberman Lander, Eric Steven |
| author_sort | Darrow, Emily M. |
| collection | MIT |
| description | During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called "superdomains," such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called "superloops." DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4 We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging. |
| first_indexed | 2024-09-23T11:47:46Z |
| format | Article |
| id | mit-1721.1/114761 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:47:46Z |
| publishDate | 2018 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1147612022-09-27T21:58:30Z Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture Darrow, Emily M. Huntley, Miriam H. Dudchenko, Olga Stamenova, Elena K. Durand, Neva C. Sun, Zhuo Huang, Su-Chen Sanborn, Adrian L. Machol, Ido Shamim, Muhammad Seberg, Andrew P. Chadwick, Brian P. Aiden, Erez Lieberman Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Lander, Eric Steven During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called "superdomains," such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called "superloops." DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4 We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging. National Human Genome Research Institute (U.S.) (Grant HG003067) 2018-04-17T17:51:38Z 2018-04-17T17:51:38Z 2016-07 2016-05 2018-04-13T19:11:47Z Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/114761 Darrow, Emily M., et al. “Deletion of DXZ4 on the Human Inactive X Chromosome Alters Higher-Order Genome Architecture.” Proceedings of the National Academy of Sciences, vol. 113, no. 31, Aug. 2016, pp. E4504–12. © 2018 National Academy of Sciences http://dx.doi.org/10.1073/PNAS.1609643113 Proceedings of the National Academy of Sciences 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 Proceedings of the National Academy of Sciences National Academy of Sciences |
| spellingShingle | Darrow, Emily M. Huntley, Miriam H. Dudchenko, Olga Stamenova, Elena K. Durand, Neva C. Sun, Zhuo Huang, Su-Chen Sanborn, Adrian L. Machol, Ido Shamim, Muhammad Seberg, Andrew P. Chadwick, Brian P. Aiden, Erez Lieberman Lander, Eric Steven Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture |
| title | Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture |
| title_full | Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture |
| title_fullStr | Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture |
| title_full_unstemmed | Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture |
| title_short | Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture |
| title_sort | deletion of dxz4 on the human inactive x chromosome alters higher order genome architecture |
| url | http://hdl.handle.net/1721.1/114761 |
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