Heterochromatin dynamics during epithelial-to-mesenchymal transition
Although heterochromatin is enriched with repressive traits, it is actively transcribed, giving rise to large amounts of non-coding RNAs. These transcripts are responsible for the formation and maintenance of heterochromatin, but little is known about how their transcription is regulated. In this th...
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| Formato: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| País: | España |
| Recursos: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/129339 |
| Acesso em linha: | http://hdl.handle.net/10803/129339 |
| Access Level: | acceso abierto |
| Palavra-chave: | Snail1 LOXL2 EMT Major satellite Heterochromatin Pericentromeric repeats Chromocenter Major satèl·lits Heterocromatina Repeticions pericentromèriques Cromocentre 576 |
| Resumo: | Although heterochromatin is enriched with repressive traits, it is actively transcribed, giving rise to large amounts of non-coding RNAs. These transcripts are responsible for the formation and maintenance of heterochromatin, but little is known about how their transcription is regulated. In this thesis we show that Snail1 transcription factor represses mouse pericentromeric transcription and regulates heterochromatin organization through the action of the H3K4 deaminase LOXL2. Snail1 has a key role in epithelial-to-mesenchymal transition (EMT). We show that, also during this process, Snail1 is responsible for pericentromeric transcription regulation. At the onset of EMT, one of the major structural heterochromatin proteins, HP1α, is transiently released from heterochromatin foci in a Snail1/LOXL2 dependent manner, concomitantly with a down-regulation of major satellite transcription. Moreover, prevention of major satellite transcripts down-regulation compromises the migratory and invasive behaviour of EMT resulting mesenchymal cells. We propose that Snail1 and LOXL2 regulate heterochromatin during this process, which may be crucial to allow the genome reorganization required to complete EMT. |
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