Spatial patterns of CTCF sites define the anatomy of TADs and their boundaries
Abstract Background Topologically associating domains (TADs) are genomic regions of self-interaction. Additionally, it is known that TAD boundaries are enriched in CTCF binding sites. In turn, CTCF sites are known to be asymmetric, whereby the convergent configuration of a pair of CTCF sites leads t...
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| Format: | Article |
| Language: | English |
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BMC
2020-08-01
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| Series: | Genome Biology |
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| Online Access: | http://link.springer.com/article/10.1186/s13059-020-02108-x |
| _version_ | 1811324567434559488 |
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| author | Luca Nanni Stefano Ceri Colin Logie |
| author_facet | Luca Nanni Stefano Ceri Colin Logie |
| author_sort | Luca Nanni |
| collection | DOAJ |
| description | Abstract Background Topologically associating domains (TADs) are genomic regions of self-interaction. Additionally, it is known that TAD boundaries are enriched in CTCF binding sites. In turn, CTCF sites are known to be asymmetric, whereby the convergent configuration of a pair of CTCF sites leads to the formation of a chromatin loop in vivo. However, to date, it has been unclear how to reconcile TAD structure with CTCF-based chromatin loops. Results We approach this problem by analysing CTCF binding site strengths and classifying clusters of CTCF sites along the genome on the basis of their relative orientation. Analysis of CTCF site orientation classes as a function of their spatial distribution along the human genome reveals that convergent CTCF site clusters are depleted while divergent CTCF clusters are enriched in the 5- to 100-kb range. We then analyse the distribution of CTCF binding sites as a function of TAD boundary conservation across seven primary human blood cell types. This reveals divergent CTCF site enrichment at TAD boundaries. Furthermore, convergent arrays of CTCF sites separate the left and right sections of TADs that harbour internal CTCF sites, resulting in unequal TAD ‘halves’. Conclusions The orientation-based CTCF binding site cluster classification that we present reconciles TAD boundaries and CTCF site clusters in a mechanistically elegant fashion. This model suggests that the emergent structure of nuclear chromatin in the form of TADs relies on the obligate alternation of divergent and convergent CTCF site clusters that occur at different length scales along the genome. Graphical abstract |
| first_indexed | 2024-04-13T14:16:35Z |
| format | Article |
| id | doaj.art-ad22a3f1a43d40b1945f9b42f3293392 |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-04-13T14:16:35Z |
| publishDate | 2020-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-ad22a3f1a43d40b1945f9b42f32933922022-12-22T02:43:38ZengBMCGenome Biology1474-760X2020-08-0121112510.1186/s13059-020-02108-xSpatial patterns of CTCF sites define the anatomy of TADs and their boundariesLuca Nanni0Stefano Ceri1Colin Logie2Department of Electronics, Information and Bioengineering (DEIB), Politecnico di MilanoDepartment of Electronics, Information and Bioengineering (DEIB), Politecnico di MilanoDepartment of Molecular Biology, Radboud Institute for Molecular Life Sciences, Faculty of Science, Radboud UniversityAbstract Background Topologically associating domains (TADs) are genomic regions of self-interaction. Additionally, it is known that TAD boundaries are enriched in CTCF binding sites. In turn, CTCF sites are known to be asymmetric, whereby the convergent configuration of a pair of CTCF sites leads to the formation of a chromatin loop in vivo. However, to date, it has been unclear how to reconcile TAD structure with CTCF-based chromatin loops. Results We approach this problem by analysing CTCF binding site strengths and classifying clusters of CTCF sites along the genome on the basis of their relative orientation. Analysis of CTCF site orientation classes as a function of their spatial distribution along the human genome reveals that convergent CTCF site clusters are depleted while divergent CTCF clusters are enriched in the 5- to 100-kb range. We then analyse the distribution of CTCF binding sites as a function of TAD boundary conservation across seven primary human blood cell types. This reveals divergent CTCF site enrichment at TAD boundaries. Furthermore, convergent arrays of CTCF sites separate the left and right sections of TADs that harbour internal CTCF sites, resulting in unequal TAD ‘halves’. Conclusions The orientation-based CTCF binding site cluster classification that we present reconciles TAD boundaries and CTCF site clusters in a mechanistically elegant fashion. This model suggests that the emergent structure of nuclear chromatin in the form of TADs relies on the obligate alternation of divergent and convergent CTCF site clusters that occur at different length scales along the genome. Graphical abstracthttp://link.springer.com/article/10.1186/s13059-020-02108-xChromatin architectureTADsTAD boundary conservationCTCF binding site clustersCTCF orientation patternsLoop extrusion |
| spellingShingle | Luca Nanni Stefano Ceri Colin Logie Spatial patterns of CTCF sites define the anatomy of TADs and their boundaries Genome Biology Chromatin architecture TADs TAD boundary conservation CTCF binding site clusters CTCF orientation patterns Loop extrusion |
| title | Spatial patterns of CTCF sites define the anatomy of TADs and their boundaries |
| title_full | Spatial patterns of CTCF sites define the anatomy of TADs and their boundaries |
| title_fullStr | Spatial patterns of CTCF sites define the anatomy of TADs and their boundaries |
| title_full_unstemmed | Spatial patterns of CTCF sites define the anatomy of TADs and their boundaries |
| title_short | Spatial patterns of CTCF sites define the anatomy of TADs and their boundaries |
| title_sort | spatial patterns of ctcf sites define the anatomy of tads and their boundaries |
| topic | Chromatin architecture TADs TAD boundary conservation CTCF binding site clusters CTCF orientation patterns Loop extrusion |
| url | http://link.springer.com/article/10.1186/s13059-020-02108-x |
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