The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist
The mouse X-inactivation center (Xic) locus represents a powerful model for understanding the links between genome architecture and gene regulation, with the non-coding genes Xist and Tsix showing opposite developmental expression patterns while being organized as an overlapping sense/antisense unit...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2019
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| _version_ | 1826266656381337600 |
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| author | Van Bemmel, J Galupa, R Gard, C Servant, N Picard, C Davies, J Szempruch, A Zhan, Y Żylicz, J Nora, E Lameiras, S De Wit, E Gentien, D Baulande, S Giorgetti, L Guttman, M Hughes, J Higgs, D Gribnau, J Heard, E |
| author_facet | Van Bemmel, J Galupa, R Gard, C Servant, N Picard, C Davies, J Szempruch, A Zhan, Y Żylicz, J Nora, E Lameiras, S De Wit, E Gentien, D Baulande, S Giorgetti, L Guttman, M Hughes, J Higgs, D Gribnau, J Heard, E |
| author_sort | Van Bemmel, J |
| collection | OXFORD |
| description | The mouse X-inactivation center (Xic) locus represents a powerful model for understanding the links between genome architecture and gene regulation, with the non-coding genes Xist and Tsix showing opposite developmental expression patterns while being organized as an overlapping sense/antisense unit. The Xic is organized into two topologically associating domains (TADs) but the role of this architecture in orchestrating cis-regulatory information remains elusive. To explore this, we generated genomic inversions that swap the Xist/Tsix transcriptional unit and place their promoters in each other's TAD. We found that this led to a switch in their expression dynamics: Xist became precociously and ectopically upregulated, both in male and female pluripotent cells, while Tsix expression aberrantly persisted during differentiation. The topological partitioning of the Xic is thus critical to ensure proper developmental timing of X inactivation. Our study illustrates how the genomic architecture of cis-regulatory landscapes can affect the regulation of mammalian developmental processes. |
| first_indexed | 2024-03-06T20:42:15Z |
| format | Journal article |
| id | oxford-uuid:34abc982-27b2-45e6-abb7-500a7cbbc14b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:42:15Z |
| publishDate | 2019 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:34abc982-27b2-45e6-abb7-500a7cbbc14b2022-03-26T13:27:25ZThe bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and XistJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:34abc982-27b2-45e6-abb7-500a7cbbc14bEnglishSymplectic Elements at OxfordSpringer Nature2019Van Bemmel, JGalupa, RGard, CServant, NPicard, CDavies, JSzempruch, AZhan, YŻylicz, JNora, ELameiras, SDe Wit, EGentien, DBaulande, SGiorgetti, LGuttman, MHughes, JHiggs, DGribnau, JHeard, EThe mouse X-inactivation center (Xic) locus represents a powerful model for understanding the links between genome architecture and gene regulation, with the non-coding genes Xist and Tsix showing opposite developmental expression patterns while being organized as an overlapping sense/antisense unit. The Xic is organized into two topologically associating domains (TADs) but the role of this architecture in orchestrating cis-regulatory information remains elusive. To explore this, we generated genomic inversions that swap the Xist/Tsix transcriptional unit and place their promoters in each other's TAD. We found that this led to a switch in their expression dynamics: Xist became precociously and ectopically upregulated, both in male and female pluripotent cells, while Tsix expression aberrantly persisted during differentiation. The topological partitioning of the Xic is thus critical to ensure proper developmental timing of X inactivation. Our study illustrates how the genomic architecture of cis-regulatory landscapes can affect the regulation of mammalian developmental processes. |
| spellingShingle | Van Bemmel, J Galupa, R Gard, C Servant, N Picard, C Davies, J Szempruch, A Zhan, Y Żylicz, J Nora, E Lameiras, S De Wit, E Gentien, D Baulande, S Giorgetti, L Guttman, M Hughes, J Higgs, D Gribnau, J Heard, E The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist |
| title | The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist |
| title_full | The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist |
| title_fullStr | The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist |
| title_full_unstemmed | The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist |
| title_short | The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist |
| title_sort | bipartite tad organization of the x inactivation center ensures opposing developmental regulation of tsix and xist |
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