The Role of macroH2A1 histone variant in muscle metabolism and development
In the eukaryotic nucleus, DNA, wrapped around a core of histone proteins. Replication-coupled histones can be exchanged by histone variants. In mammals, H2A can be replaced by three distinct macroH2A proteins. Alternative splicing of the macroH2A1 transcript further gives rise to macroH2A1.1 and ma...
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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:10803/667572 |
| Acceso en línea: | http://hdl.handle.net/10803/667572 |
| Access Level: | acceso abierto |
| Palabra clave: | Histone MacroH2A PARPI Metabolism Muscle Histona Metabolismo Músculo 575 |
| Sumario: | In the eukaryotic nucleus, DNA, wrapped around a core of histone proteins. Replication-coupled histones can be exchanged by histone variants. In mammals, H2A can be replaced by three distinct macroH2A proteins. Alternative splicing of the macroH2A1 transcript further gives rise to macroH2A1.1 and macroH2A1.2 isoforms. We discovered that the expression of macroH2A1 splice isoforms switch during myogenic differentiation. From predominant expression of macroH2A1.2 in proliferating myoblasts to high expression of macroH2A1.1 in differentiated myotubes. This switch has two major consequences. First, both isoforms differentially regulate a number of genes and the dynamics of cell fusion. Second, macroH2A1.1 impacts on cellular metabolism by binding and inhibiting the major nicotinamide adenine dinucleotide-consuming enzyme in the nucleus, the cellular stress sensor PARP1. Finally, we provide evidence that the PARP1 inhibitory capacity of macroH2A is an ancestral function of the protein ranging back to the origins of multicellular life. |
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