Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver
CTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present and validate a computational method to predict cohesin-and-CTCF binding sites that form intra-TAD DNA loops. The intra-TAD loop...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/34077 |
| _version_ | 1811181140607762432 |
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| author | Bryan J Matthews David J Waxman |
| author_facet | Bryan J Matthews David J Waxman |
| author_sort | Bryan J Matthews |
| collection | DOAJ |
| description | CTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present and validate a computational method to predict cohesin-and-CTCF binding sites that form intra-TAD DNA loops. The intra-TAD loop anchors identified are structurally indistinguishable from TAD anchors regarding binding partners, sequence conservation, and resistance to cohesin knockdown; further, the intra-TAD loops retain key functional features of TADs, including chromatin contact insulation, blockage of repressive histone mark spread, and ubiquity across tissues. We propose that intra-TAD loops form by the same loop extrusion mechanism as the larger TAD loops, and that their shorter length enables finer regulatory control in restricting enhancer-promoter interactions, which enables selective, high-level expression of gene targets of super-enhancers and genes located within repressive nuclear compartments. These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization associated with widespread insulation of distal enhancer activity. |
| first_indexed | 2024-04-11T09:13:40Z |
| format | Article |
| id | doaj.art-375d95ffe0f54864aae4d0ca50f3a8c5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:13:40Z |
| publishDate | 2018-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-375d95ffe0f54864aae4d0ca50f3a8c52022-12-22T04:32:25ZengeLife Sciences Publications LtdeLife2050-084X2018-05-01710.7554/eLife.34077Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liverBryan J Matthews0https://orcid.org/0000-0002-1930-339XDavid J Waxman1https://orcid.org/0000-0001-7982-9206Department of Biology and Bioinformatics Program, Boston University, Boston, United StatesDepartment of Biology and Bioinformatics Program, Boston University, Boston, United StatesCTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present and validate a computational method to predict cohesin-and-CTCF binding sites that form intra-TAD DNA loops. The intra-TAD loop anchors identified are structurally indistinguishable from TAD anchors regarding binding partners, sequence conservation, and resistance to cohesin knockdown; further, the intra-TAD loops retain key functional features of TADs, including chromatin contact insulation, blockage of repressive histone mark spread, and ubiquity across tissues. We propose that intra-TAD loops form by the same loop extrusion mechanism as the larger TAD loops, and that their shorter length enables finer regulatory control in restricting enhancer-promoter interactions, which enables selective, high-level expression of gene targets of super-enhancers and genes located within repressive nuclear compartments. These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization associated with widespread insulation of distal enhancer activity.https://elifesciences.org/articles/34077chromatin domainscompartmentalizationnuclear organization |
| spellingShingle | Bryan J Matthews David J Waxman Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver eLife chromatin domains compartmentalization nuclear organization |
| title | Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver |
| title_full | Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver |
| title_fullStr | Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver |
| title_full_unstemmed | Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver |
| title_short | Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver |
| title_sort | computational prediction of ctcf cohesin based intra tad loops that insulate chromatin contacts and gene expression in mouse liver |
| topic | chromatin domains compartmentalization nuclear organization |
| url | https://elifesciences.org/articles/34077 |
| work_keys_str_mv | AT bryanjmatthews computationalpredictionofctcfcohesinbasedintratadloopsthatinsulatechromatincontactsandgeneexpressioninmouseliver AT davidjwaxman computationalpredictionofctcfcohesinbasedintratadloopsthatinsulatechromatincontactsandgeneexpressioninmouseliver |