CTCF as a boundary factor for cohesin-mediated loop extrusion: evidence for a multi-step mechanism
© 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Mammalian genome structure is closely linked to function. At the scale of kilobases to megabases, CTCF and cohesin organize the genome into chromatin loops. Mechanistically, cohesin is proposed to...
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| Format: | Article |
| Language: | English |
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Informa UK Limited
2021
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| Online Access: | https://hdl.handle.net/1721.1/133517 |
| _version_ | 1826204358130270208 |
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| author | Hansen, Anders S |
| author_facet | Hansen, Anders S |
| author_sort | Hansen, Anders S |
| collection | MIT |
| description | © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Mammalian genome structure is closely linked to function. At the scale of kilobases to megabases, CTCF and cohesin organize the genome into chromatin loops. Mechanistically, cohesin is proposed to extrude chromatin loops bidirectionally until it encounters occupied CTCF DNA-binding sites. Curiously, loops form predominantly between CTCF binding sites in a convergent orientation. How CTCF interacts with and blocks cohesin extrusion in an orientation-specific manner has remained a mechanistic mystery. Here, we review recent papers that have shed light on these processes and suggest a multi-step interaction between CTCF and cohesin. This interaction may first involve a pausing step, where CTCF halts cohesin extrusion, followed by a stabilization step of the CTCF-cohesin complex, resulting in a chromatin loop. Finally, we discuss our own recent studies on an internal RNA-Binding Region (RBRi) in CTCF to elucidate its role in regulating CTCF clustering, target search mechanisms and chromatin loop formation and future challenges. |
| first_indexed | 2024-09-23T12:53:05Z |
| format | Article |
| id | mit-1721.1/133517 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:53:05Z |
| publishDate | 2021 |
| publisher | Informa UK Limited |
| record_format | dspace |
| spelling | mit-1721.1/1335172021-10-27T19:54:46Z CTCF as a boundary factor for cohesin-mediated loop extrusion: evidence for a multi-step mechanism Hansen, Anders S © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Mammalian genome structure is closely linked to function. At the scale of kilobases to megabases, CTCF and cohesin organize the genome into chromatin loops. Mechanistically, cohesin is proposed to extrude chromatin loops bidirectionally until it encounters occupied CTCF DNA-binding sites. Curiously, loops form predominantly between CTCF binding sites in a convergent orientation. How CTCF interacts with and blocks cohesin extrusion in an orientation-specific manner has remained a mechanistic mystery. Here, we review recent papers that have shed light on these processes and suggest a multi-step interaction between CTCF and cohesin. This interaction may first involve a pausing step, where CTCF halts cohesin extrusion, followed by a stabilization step of the CTCF-cohesin complex, resulting in a chromatin loop. Finally, we discuss our own recent studies on an internal RNA-Binding Region (RBRi) in CTCF to elucidate its role in regulating CTCF clustering, target search mechanisms and chromatin loop formation and future challenges. 2021-10-27T19:53:18Z 2021-10-27T19:53:18Z 2020 2021-08-27T18:19:50Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133517 en 10.1080/19491034.2020.1782024 Nucleus Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/octet-stream Informa UK Limited Taylor & Francis |
| spellingShingle | Hansen, Anders S CTCF as a boundary factor for cohesin-mediated loop extrusion: evidence for a multi-step mechanism |
| title | CTCF as a boundary factor for cohesin-mediated loop extrusion: evidence for a multi-step mechanism |
| title_full | CTCF as a boundary factor for cohesin-mediated loop extrusion: evidence for a multi-step mechanism |
| title_fullStr | CTCF as a boundary factor for cohesin-mediated loop extrusion: evidence for a multi-step mechanism |
| title_full_unstemmed | CTCF as a boundary factor for cohesin-mediated loop extrusion: evidence for a multi-step mechanism |
| title_short | CTCF as a boundary factor for cohesin-mediated loop extrusion: evidence for a multi-step mechanism |
| title_sort | ctcf as a boundary factor for cohesin mediated loop extrusion evidence for a multi step mechanism |
| url | https://hdl.handle.net/1721.1/133517 |
| work_keys_str_mv | AT hansenanderss ctcfasaboundaryfactorforcohesinmediatedloopextrusionevidenceforamultistepmechanism |