Snail1 controls telomere integrity and transcription and telomerase expression

Snail1 transcription factor is the key inducer of epithelial-to-mesenchymal transition (EMT). Here, we describe a novel role for Snail1 on the regulation of telomere integrity and transcription as well as telomerase expression. FISH assays indicate an increase of telomere alterations in Snail1-deple...

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Detalles Bibliográficos
Autor: Gonzàlez Busqué, Núria
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/663193
Acceso en línea:http://hdl.handle.net/10803/663193
Access Level:acceso abierto
Palabra clave:Snail1
TERRA
EMT
Caspase
Telomerasa
Heterocromatina
Inflamació
Càncer
576
Descripción
Sumario:Snail1 transcription factor is the key inducer of epithelial-to-mesenchymal transition (EMT). Here, we describe a novel role for Snail1 on the regulation of telomere integrity and transcription as well as telomerase expression. FISH assays indicate an increase of telomere alterations in Snail1-depleted mouse mesenchymal stem cells (MSCs) and shorter telomeres. However, these cells present higher levels of TERT since Snail1 represses its expression, meaning that other mechanisms in telomere homeostasis are involved. In fact, telomeres are transcribed into a long non-coding RNA called telomeric repeat-containing RNA (TERRA). Here we report that Snail1 regulates TERRA transcription by repressing TERRA 2q, 11q and 18q. TERRA and TERT are transiently down-regulated during EMT in NMuMG cells. Ectopic expression of TERRA affects the transcription of some genes induced during EMT such as fibronectin whereas TERT does not modify those genes. We propose that Snail1 control of TERRA besides being required for telomere maintenance is also necessary for the expression of a subset of mesenchymal genes.