Multi-scale study of the genome architecture and its dynamical facets
High-throughput Chromosome Conformation Capture (3C) techniques have provided a comprehensive overview of the genome architecture. Hi-C, a derivative of 3C, has become a reference technique to study the 3D chromatin structure and its relationship with the functional state of the cell. However, sever...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/668229 |
| Acceso en línea: | http://hdl.handle.net/10803/668229 |
| Access Level: | acceso abierto |
| Palabra clave: | Genome architecture Hi-C Chromatin compartments Tipollogycally-associated domains TADpole Arquitectura genòmica Compartimentos de la cromatina Dominios asociados topológicamente 575 |
| Sumario: | High-throughput Chromosome Conformation Capture (3C) techniques have provided a comprehensive overview of the genome architecture. Hi-C, a derivative of 3C, has become a reference technique to study the 3D chromatin structure and its relationship with the functional state of the cell. However, several aspects of the analysis and interpretation of Hi-C data remain a challenge and may hide a potential yet to be unveiled. In this thesis, we explore the structural landscape of multiple chromatin features. We developed an integrative approach combining in situ Hi-C data with nine additional omic layers and revealed a new dynamic and transitional genomic compartment enriched in poised and polycomb-repressed chromatin. This novel intermediate compartment plays an important role in the modulation of the genome during B cells differentiation and upon neoplastic transformation, specifically in chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) patients. We also developed TADpole, a computational tool designed to characterize the hierarchy of topologically-associated domains (TADs) using Hi-C interaction matrices. We demonstrated its technical and biological robustness, and its capacity to reveal topological differences in high-resolution capture Hi-C experiments. |
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