A dynamic folded Hairpin conformation is associated with α-Globin activation in Erythroid cells
We investigate the three-dimensional (3D) conformations of the α-globin locus at the single-allele level in murine embryonic stem cells (ESCs) and erythroid cells, combining polymer physics models and high-resolution Capture-C data. Model predictions are validated against independent fluorescence in...
| Asıl Yazarlar: | , , , , , , , , , , , , , , , , |
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| Materyal Türü: | Journal article |
| Dil: | English |
| Baskı/Yayın Bilgisi: |
Elsevier (Cell Press)
2020
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| _version_ | 1826297311749210112 |
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| author | Chiariello, AM Bianco, S Oudelaar, AM Esposito, A Annunziatella, C Fiorillo, L Conte, M Corrado, A Prisco, A Larke, MSC Telenius, JM Sciarretta, R Musella, F Buckle, VJ Higgs, DR Hughes, JR Nicodemi, M |
| author_facet | Chiariello, AM Bianco, S Oudelaar, AM Esposito, A Annunziatella, C Fiorillo, L Conte, M Corrado, A Prisco, A Larke, MSC Telenius, JM Sciarretta, R Musella, F Buckle, VJ Higgs, DR Hughes, JR Nicodemi, M |
| author_sort | Chiariello, AM |
| collection | OXFORD |
| description | We investigate the three-dimensional (3D) conformations of the α-globin locus at the single-allele level in murine embryonic stem cells (ESCs) and erythroid cells, combining polymer physics models and high-resolution Capture-C data. Model predictions are validated against independent fluorescence in situ hybridization (FISH) data measuring pairwise distances, and Tri-C data identifying three-way contacts. The architecture is rearranged during the transition from ESCs to erythroid cells, associated with the activation of the globin genes. We find that in ESCs, the spatial organization conforms to a highly intermingled 3D structure involving non-specific contacts, whereas in erythroid cells the α-globin genes and their enhancers form a self-contained domain, arranged in a folded hairpin conformation, separated from intermingling flanking regions by a thermodynamic mechanism of micro-phase separation. The flanking regions are rich in convergent CTCF sites, which only marginally participate in the erythroid-specific gene-enhancer contacts, suggesting that beyond the interaction of CTCF sites, multiple molecular mechanisms cooperate to form an interacting domain. |
| first_indexed | 2024-03-07T04:29:39Z |
| format | Journal article |
| id | oxford-uuid:cde0fbc6-e3c9-4b02-aec0-9863a1d9f2b7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:29:39Z |
| publishDate | 2020 |
| publisher | Elsevier (Cell Press) |
| record_format | dspace |
| spelling | oxford-uuid:cde0fbc6-e3c9-4b02-aec0-9863a1d9f2b72022-03-27T07:31:54ZA dynamic folded Hairpin conformation is associated with α-Globin activation in Erythroid cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cde0fbc6-e3c9-4b02-aec0-9863a1d9f2b7EnglishSymplectic ElementsElsevier (Cell Press)2020Chiariello, AMBianco, SOudelaar, AMEsposito, AAnnunziatella, CFiorillo, LConte, MCorrado, APrisco, ALarke, MSCTelenius, JMSciarretta, RMusella, FBuckle, VJHiggs, DRHughes, JRNicodemi, MWe investigate the three-dimensional (3D) conformations of the α-globin locus at the single-allele level in murine embryonic stem cells (ESCs) and erythroid cells, combining polymer physics models and high-resolution Capture-C data. Model predictions are validated against independent fluorescence in situ hybridization (FISH) data measuring pairwise distances, and Tri-C data identifying three-way contacts. The architecture is rearranged during the transition from ESCs to erythroid cells, associated with the activation of the globin genes. We find that in ESCs, the spatial organization conforms to a highly intermingled 3D structure involving non-specific contacts, whereas in erythroid cells the α-globin genes and their enhancers form a self-contained domain, arranged in a folded hairpin conformation, separated from intermingling flanking regions by a thermodynamic mechanism of micro-phase separation. The flanking regions are rich in convergent CTCF sites, which only marginally participate in the erythroid-specific gene-enhancer contacts, suggesting that beyond the interaction of CTCF sites, multiple molecular mechanisms cooperate to form an interacting domain. |
| spellingShingle | Chiariello, AM Bianco, S Oudelaar, AM Esposito, A Annunziatella, C Fiorillo, L Conte, M Corrado, A Prisco, A Larke, MSC Telenius, JM Sciarretta, R Musella, F Buckle, VJ Higgs, DR Hughes, JR Nicodemi, M A dynamic folded Hairpin conformation is associated with α-Globin activation in Erythroid cells |
| title | A dynamic folded Hairpin conformation is associated with α-Globin activation in Erythroid cells |
| title_full | A dynamic folded Hairpin conformation is associated with α-Globin activation in Erythroid cells |
| title_fullStr | A dynamic folded Hairpin conformation is associated with α-Globin activation in Erythroid cells |
| title_full_unstemmed | A dynamic folded Hairpin conformation is associated with α-Globin activation in Erythroid cells |
| title_short | A dynamic folded Hairpin conformation is associated with α-Globin activation in Erythroid cells |
| title_sort | dynamic folded hairpin conformation is associated with α globin activation in erythroid cells |
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