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High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion dynamics
DNA looping is vital for establishing many enhancer-promoter interactions. While CTCF is known to anchor many cohesin-mediated loops, the looped chromatin fiber appears to predominantly exist in a poorly characterized actively extruding state. To better characterize extruding chromatin loop structur...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634716/ https://www.ncbi.nlm.nih.gov/pubmed/37961446 http://dx.doi.org/10.1101/2023.10.20.563340 |
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author | Sept, Corriene E. Tak, Y. Esther Cerda-Smith, Christian G. Hutchinson, Haley M. Goel, Viraat Blanchette, Marco Bhakta, Mital S. Hansen, Anders S. Joung, J. Keith Johnstone, Sarah Eyler, Christine E. Aryee, Martin J. |
author_facet | Sept, Corriene E. Tak, Y. Esther Cerda-Smith, Christian G. Hutchinson, Haley M. Goel, Viraat Blanchette, Marco Bhakta, Mital S. Hansen, Anders S. Joung, J. Keith Johnstone, Sarah Eyler, Christine E. Aryee, Martin J. |
author_sort | Sept, Corriene E. |
collection | PubMed |
description | DNA looping is vital for establishing many enhancer-promoter interactions. While CTCF is known to anchor many cohesin-mediated loops, the looped chromatin fiber appears to predominantly exist in a poorly characterized actively extruding state. To better characterize extruding chromatin loop structures, we used CTCF MNase HiChIP data to determine both CTCF binding at high resolution and 3D contact information. Here we present FactorFinder, a tool that identifies CTCF binding sites at near base-pair resolution. We leverage this substantial advance in resolution to determine that the fully extruded (CTCF-CTCF) state is rare genome-wide with locus-specific variation from ~1–10%. We further investigate the impact of chromatin state on loop extrusion dynamics, and find that active enhancers and RNA Pol II impede cohesin extrusion, facilitating an enrichment of enhancer-promoter contacts in the partially extruded loop state. We propose a model of topological regulation whereby the transient, partially extruded states play active roles in transcription. |
format | Online Article Text |
id | pubmed-10634716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-106347162023-11-13 High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion dynamics Sept, Corriene E. Tak, Y. Esther Cerda-Smith, Christian G. Hutchinson, Haley M. Goel, Viraat Blanchette, Marco Bhakta, Mital S. Hansen, Anders S. Joung, J. Keith Johnstone, Sarah Eyler, Christine E. Aryee, Martin J. bioRxiv Article DNA looping is vital for establishing many enhancer-promoter interactions. While CTCF is known to anchor many cohesin-mediated loops, the looped chromatin fiber appears to predominantly exist in a poorly characterized actively extruding state. To better characterize extruding chromatin loop structures, we used CTCF MNase HiChIP data to determine both CTCF binding at high resolution and 3D contact information. Here we present FactorFinder, a tool that identifies CTCF binding sites at near base-pair resolution. We leverage this substantial advance in resolution to determine that the fully extruded (CTCF-CTCF) state is rare genome-wide with locus-specific variation from ~1–10%. We further investigate the impact of chromatin state on loop extrusion dynamics, and find that active enhancers and RNA Pol II impede cohesin extrusion, facilitating an enrichment of enhancer-promoter contacts in the partially extruded loop state. We propose a model of topological regulation whereby the transient, partially extruded states play active roles in transcription. Cold Spring Harbor Laboratory 2023-10-28 /pmc/articles/PMC10634716/ /pubmed/37961446 http://dx.doi.org/10.1101/2023.10.20.563340 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Sept, Corriene E. Tak, Y. Esther Cerda-Smith, Christian G. Hutchinson, Haley M. Goel, Viraat Blanchette, Marco Bhakta, Mital S. Hansen, Anders S. Joung, J. Keith Johnstone, Sarah Eyler, Christine E. Aryee, Martin J. High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion dynamics |
title | High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion dynamics |
title_full | High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion dynamics |
title_fullStr | High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion dynamics |
title_full_unstemmed | High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion dynamics |
title_short | High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion dynamics |
title_sort | high-resolution ctcf footprinting reveals impact of chromatin state on cohesin extrusion dynamics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634716/ https://www.ncbi.nlm.nih.gov/pubmed/37961446 http://dx.doi.org/10.1101/2023.10.20.563340 |
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