Active regulatory elements recruit cohesin to establish cell specific chromatin domains
Abstract As the 3D structure of the genome is analysed at ever increasing resolution it is clear that there is considerable variation in the 3D chromatin architecture across different cell types. It has been proposed that this may, in part, be due to increased recruitment of cohesin to activated cis...
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Nature Portfolio
2025-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-96248-4 |
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| author | Emily Georgiades Caroline Harrold Nigel Roberts Mira Kassouf Simone G. Riva Edward Sanders Damien Downes Helena S. Francis Joseph Blayney A. Marieke Oudelaar Thomas A. Milne Douglas Higgs Jim R. Hughes |
| author_facet | Emily Georgiades Caroline Harrold Nigel Roberts Mira Kassouf Simone G. Riva Edward Sanders Damien Downes Helena S. Francis Joseph Blayney A. Marieke Oudelaar Thomas A. Milne Douglas Higgs Jim R. Hughes |
| author_sort | Emily Georgiades |
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| description | Abstract As the 3D structure of the genome is analysed at ever increasing resolution it is clear that there is considerable variation in the 3D chromatin architecture across different cell types. It has been proposed that this may, in part, be due to increased recruitment of cohesin to activated cis-elements (enhancers and promoters) leading to cell-type specific loop extrusion underlying the formation of new sub-TADs. Here we show that cohesin correlates well with the presence of active enhancers and that this varies in an allele-specific manner with the presence or absence of polymorphic enhancers which vary from one individual to another. Using the alpha globin cluster as a model, we show that when all enhancers are removed, peaks of cohesin disappear from these regions and the erythroid specific sub-TAD is no longer formed. Re-insertion of the major alpha globin enhancer (R2) is associated with re-establishment of recruitment and increased interactions. In complementary experiments insertion of the R2 enhancer element into a “neutral” region of the genome recruits cohesin, induces transcription and creates a new large (75 kb) erythroid-specific domain. Together these findings support the proposal that active enhancers recruit cohesin, stimulate loop extrusion and promote the formation of cell specific sub-TADs. |
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| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-fd697431a2c04f8ca8d8ac5a962cffb82025-08-20T02:17:09ZengNature PortfolioScientific Reports2045-23222025-04-0115111610.1038/s41598-025-96248-4Active regulatory elements recruit cohesin to establish cell specific chromatin domainsEmily Georgiades0Caroline Harrold1Nigel Roberts2Mira Kassouf3Simone G. Riva4Edward Sanders5Damien Downes6Helena S. Francis7Joseph Blayney8A. Marieke Oudelaar9Thomas A. Milne10Douglas Higgs11Jim R. Hughes12MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of OxfordMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of OxfordMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of OxfordMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of OxfordMRC WIMM Centre for Computational Biology, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of OxfordMRC WIMM Centre for Computational Biology, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of OxfordMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of OxfordMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of OxfordMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of OxfordMax Planck Institute for Multidisciplinary SciencesMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of OxfordMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of OxfordMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of OxfordAbstract As the 3D structure of the genome is analysed at ever increasing resolution it is clear that there is considerable variation in the 3D chromatin architecture across different cell types. It has been proposed that this may, in part, be due to increased recruitment of cohesin to activated cis-elements (enhancers and promoters) leading to cell-type specific loop extrusion underlying the formation of new sub-TADs. Here we show that cohesin correlates well with the presence of active enhancers and that this varies in an allele-specific manner with the presence or absence of polymorphic enhancers which vary from one individual to another. Using the alpha globin cluster as a model, we show that when all enhancers are removed, peaks of cohesin disappear from these regions and the erythroid specific sub-TAD is no longer formed. Re-insertion of the major alpha globin enhancer (R2) is associated with re-establishment of recruitment and increased interactions. In complementary experiments insertion of the R2 enhancer element into a “neutral” region of the genome recruits cohesin, induces transcription and creates a new large (75 kb) erythroid-specific domain. Together these findings support the proposal that active enhancers recruit cohesin, stimulate loop extrusion and promote the formation of cell specific sub-TADs.https://doi.org/10.1038/s41598-025-96248-4 |
| spellingShingle | Emily Georgiades Caroline Harrold Nigel Roberts Mira Kassouf Simone G. Riva Edward Sanders Damien Downes Helena S. Francis Joseph Blayney A. Marieke Oudelaar Thomas A. Milne Douglas Higgs Jim R. Hughes Active regulatory elements recruit cohesin to establish cell specific chromatin domains Scientific Reports |
| title | Active regulatory elements recruit cohesin to establish cell specific chromatin domains |
| title_full | Active regulatory elements recruit cohesin to establish cell specific chromatin domains |
| title_fullStr | Active regulatory elements recruit cohesin to establish cell specific chromatin domains |
| title_full_unstemmed | Active regulatory elements recruit cohesin to establish cell specific chromatin domains |
| title_short | Active regulatory elements recruit cohesin to establish cell specific chromatin domains |
| title_sort | active regulatory elements recruit cohesin to establish cell specific chromatin domains |
| url | https://doi.org/10.1038/s41598-025-96248-4 |
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