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CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention
The DNA-binding protein CCCTC-binding factor (CTCF) and the cohesin complex function together to shape chromatin architecture in mammalian cells, but the molecular details of this process remain unclear. Here, we demonstrate that a 79-aa region within the CTCF N terminus is essential for cohesin pos...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995019/ https://www.ncbi.nlm.nih.gov/pubmed/31937660 http://dx.doi.org/10.1073/pnas.1911708117 |
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author | Pugacheva, Elena M. Kubo, Naoki Loukinov, Dmitri Tajmul, Md Kang, Sungyun Kovalchuk, Alexander L. Strunnikov, Alexander V. Zentner, Gabriel E. Ren, Bing Lobanenkov, Victor V. |
author_facet | Pugacheva, Elena M. Kubo, Naoki Loukinov, Dmitri Tajmul, Md Kang, Sungyun Kovalchuk, Alexander L. Strunnikov, Alexander V. Zentner, Gabriel E. Ren, Bing Lobanenkov, Victor V. |
author_sort | Pugacheva, Elena M. |
collection | PubMed |
description | The DNA-binding protein CCCTC-binding factor (CTCF) and the cohesin complex function together to shape chromatin architecture in mammalian cells, but the molecular details of this process remain unclear. Here, we demonstrate that a 79-aa region within the CTCF N terminus is essential for cohesin positioning at CTCF binding sites and chromatin loop formation. However, the N terminus of CTCF fused to artificial zinc fingers was not sufficient to redirect cohesin to non-CTCF binding sites, indicating a lack of an autonomously functioning domain in CTCF responsible for cohesin positioning. BORIS (CTCFL), a germline-specific paralog of CTCF, was unable to anchor cohesin to CTCF DNA binding sites. Furthermore, CTCF–BORIS chimeric constructs provided evidence that, besides the N terminus of CTCF, the first two CTCF zinc fingers, and likely the 3D geometry of CTCF–DNA complexes, are also involved in cohesin retention. Based on this knowledge, we were able to convert BORIS into CTCF with respect to cohesin positioning, thus providing additional molecular details of the ability of CTCF to retain cohesin. Taken together, our data provide insight into the process by which DNA-bound CTCF constrains cohesin movement to shape spatiotemporal genome organization. |
format | Online Article Text |
id | pubmed-6995019 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-69950192020-02-05 CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention Pugacheva, Elena M. Kubo, Naoki Loukinov, Dmitri Tajmul, Md Kang, Sungyun Kovalchuk, Alexander L. Strunnikov, Alexander V. Zentner, Gabriel E. Ren, Bing Lobanenkov, Victor V. Proc Natl Acad Sci U S A Biological Sciences The DNA-binding protein CCCTC-binding factor (CTCF) and the cohesin complex function together to shape chromatin architecture in mammalian cells, but the molecular details of this process remain unclear. Here, we demonstrate that a 79-aa region within the CTCF N terminus is essential for cohesin positioning at CTCF binding sites and chromatin loop formation. However, the N terminus of CTCF fused to artificial zinc fingers was not sufficient to redirect cohesin to non-CTCF binding sites, indicating a lack of an autonomously functioning domain in CTCF responsible for cohesin positioning. BORIS (CTCFL), a germline-specific paralog of CTCF, was unable to anchor cohesin to CTCF DNA binding sites. Furthermore, CTCF–BORIS chimeric constructs provided evidence that, besides the N terminus of CTCF, the first two CTCF zinc fingers, and likely the 3D geometry of CTCF–DNA complexes, are also involved in cohesin retention. Based on this knowledge, we were able to convert BORIS into CTCF with respect to cohesin positioning, thus providing additional molecular details of the ability of CTCF to retain cohesin. Taken together, our data provide insight into the process by which DNA-bound CTCF constrains cohesin movement to shape spatiotemporal genome organization. National Academy of Sciences 2020-01-28 2020-01-14 /pmc/articles/PMC6995019/ /pubmed/31937660 http://dx.doi.org/10.1073/pnas.1911708117 Text en Copyright © 2020 the Author(s). Published by PNAS. http://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Biological Sciences Pugacheva, Elena M. Kubo, Naoki Loukinov, Dmitri Tajmul, Md Kang, Sungyun Kovalchuk, Alexander L. Strunnikov, Alexander V. Zentner, Gabriel E. Ren, Bing Lobanenkov, Victor V. CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention |
title | CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention |
title_full | CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention |
title_fullStr | CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention |
title_full_unstemmed | CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention |
title_short | CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention |
title_sort | ctcf mediates chromatin looping via n-terminal domain-dependent cohesin retention |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995019/ https://www.ncbi.nlm.nih.gov/pubmed/31937660 http://dx.doi.org/10.1073/pnas.1911708117 |
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