Evolutionary interplay between epigenetic regulation and gene expression dynamics in human and other primates
The evolution of the human phenotype involved gene regulatory innovations. Comparative functional epigenomic studies are a powerful tool with potential to shed light on many long-standing questions regarding human evolution. Yet, despite explosive growth of human epigenome data, analogous datasets i...
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| Formato: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Recursos: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/665992 |
| Acesso em linha: | http://hdl.handle.net/10803/665992 |
| Access Level: | acceso abierto |
| Palavra-chave: | Evolution Epigenome Gene regulation Primates Evolución Epigenoma Regulación génica 575 |
| Resumo: | The evolution of the human phenotype involved gene regulatory innovations. Comparative functional epigenomic studies are a powerful tool with potential to shed light on many long-standing questions regarding human evolution. Yet, despite explosive growth of human epigenome data, analogous datasets in non-human primate species are scarce, which hampers the advancement of the field. In this work, we have characterized the evolutionary dynamics of regulatory elements in the primate lineage. To that end, we have conducted a comprehensive chromatin profiling along with downstream expression levels of lymphoblastoid cell lines (LCLs) from human, chimpanzee, gorilla, orangutan and macaque. Beyond providing a valuable resource for the scientific community (we report the first non-human primate reference epigenomes) we use this suitable multi-omics dataset to investigate regulatory differences in human evolution. We find different evolutionary patterns of change in promoters and enhancers, which are strongly dependent on the activity state. We also report that genes with variable gene expression across species are enriched in those that do not conserve their regulatory architecture, highlighting the importance of genic enhancers in lineage-specific divergence. Further, we are able to link concrete epigenomic changes in gene-architectural components with different expression evolutionary trajectories and associate the type of epigenomic change with the magnitude of the shift in expression levels. |
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