Molecular basis of CTCF binding polarity in genome folding
© 2020, The Author(s). Current models propose that boundaries of mammalian topologically associating domains (TADs) arise from the ability of the CTCF protein to stop extrusion of chromatin loops by cohesin. While the orientation of CTCF motifs determines which pairs of CTCF sites preferentially sta...
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Language: | English |
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Springer Science and Business Media LLC
2021
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Online Access: | https://hdl.handle.net/1721.1/138402 |
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author | Nora, Elphège P Caccianini, Laura Fudenberg, Geoffrey So, Kevin Kameswaran, Vasumathi Nagle, Abigail Uebersohn, Alec Hajj, Bassam Saux, Agnès Le Coulon, Antoine Mirny, Leonid A Pollard, Katherine S Dahan, Maxime Bruneau, Benoit G |
author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Nora, Elphège P Caccianini, Laura Fudenberg, Geoffrey So, Kevin Kameswaran, Vasumathi Nagle, Abigail Uebersohn, Alec Hajj, Bassam Saux, Agnès Le Coulon, Antoine Mirny, Leonid A Pollard, Katherine S Dahan, Maxime Bruneau, Benoit G |
author_sort | Nora, Elphège P |
collection | MIT |
description | © 2020, The Author(s). Current models propose that boundaries of mammalian topologically associating domains (TADs) arise from the ability of the CTCF protein to stop extrusion of chromatin loops by cohesin. While the orientation of CTCF motifs determines which pairs of CTCF sites preferentially stabilize loops, the molecular basis of this polarity remains unclear. By combining ChIP-seq and single molecule live imaging we report that CTCF positions cohesin, but does not control its overall binding dynamics on chromatin. Using an inducible complementation system, we find that CTCF mutants lacking the N-terminus cannot insulate TADs properly. Cohesin remains at CTCF sites in this mutant, albeit with reduced enrichment. Given the orientation of CTCF motifs presents the N-terminus towards cohesin as it translocates from the interior of TADs, these observations explain how the orientation of CTCF binding sites translates into genome folding patterns. |
first_indexed | 2024-09-23T15:58:16Z |
format | Article |
id | mit-1721.1/138402 |
institution | Massachusetts Institute of Technology |
language | English |
last_indexed | 2024-09-23T15:58:16Z |
publishDate | 2021 |
publisher | Springer Science and Business Media LLC |
record_format | dspace |
spelling | mit-1721.1/1384022024-03-19T14:09:31Z Molecular basis of CTCF binding polarity in genome folding Nora, Elphège P Caccianini, Laura Fudenberg, Geoffrey So, Kevin Kameswaran, Vasumathi Nagle, Abigail Uebersohn, Alec Hajj, Bassam Saux, Agnès Le Coulon, Antoine Mirny, Leonid A Pollard, Katherine S Dahan, Maxime Bruneau, Benoit G Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Physics © 2020, The Author(s). Current models propose that boundaries of mammalian topologically associating domains (TADs) arise from the ability of the CTCF protein to stop extrusion of chromatin loops by cohesin. While the orientation of CTCF motifs determines which pairs of CTCF sites preferentially stabilize loops, the molecular basis of this polarity remains unclear. By combining ChIP-seq and single molecule live imaging we report that CTCF positions cohesin, but does not control its overall binding dynamics on chromatin. Using an inducible complementation system, we find that CTCF mutants lacking the N-terminus cannot insulate TADs properly. Cohesin remains at CTCF sites in this mutant, albeit with reduced enrichment. Given the orientation of CTCF motifs presents the N-terminus towards cohesin as it translocates from the interior of TADs, these observations explain how the orientation of CTCF binding sites translates into genome folding patterns. 2021-12-09T13:18:22Z 2021-12-09T13:18:22Z 2020 2021-12-09T13:15:19Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/138402 Nora, Elphège P, Caccianini, Laura, Fudenberg, Geoffrey, So, Kevin, Kameswaran, Vasumathi et al. 2020. "Molecular basis of CTCF binding polarity in genome folding." Nature Communications, 11 (1). en 10.1038/S41467-020-19283-X Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
spellingShingle | Nora, Elphège P Caccianini, Laura Fudenberg, Geoffrey So, Kevin Kameswaran, Vasumathi Nagle, Abigail Uebersohn, Alec Hajj, Bassam Saux, Agnès Le Coulon, Antoine Mirny, Leonid A Pollard, Katherine S Dahan, Maxime Bruneau, Benoit G Molecular basis of CTCF binding polarity in genome folding |
title | Molecular basis of CTCF binding polarity in genome folding |
title_full | Molecular basis of CTCF binding polarity in genome folding |
title_fullStr | Molecular basis of CTCF binding polarity in genome folding |
title_full_unstemmed | Molecular basis of CTCF binding polarity in genome folding |
title_short | Molecular basis of CTCF binding polarity in genome folding |
title_sort | molecular basis of ctcf binding polarity in genome folding |
url | https://hdl.handle.net/1721.1/138402 |
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