EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21

The function of EZH2 as a transcription repressor is well characterized. However, its role during vertebrate development is still poorly understood, particularly in neurogenesis. Here, we uncover the role of EZH2 in controlling the integrity of the neural tube and allowing proper progenitor prolifer...

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Detalles Bibliográficos
Autores: Akizu, Naiara, García, María Alejandra, Estarás, Conchi, Fueyo, Raquel, Badosa, Carmen, Cruz, Xavier de la, Martínez-Balbás, Marian
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/133759
Acceso en línea:http://hdl.handle.net/10261/133759
Access Level:acceso abierto
Palabra clave:Neuroblast proliferation
Neural development
EZH2
Gene silencing
Histone methylation
Descripción
Sumario:The function of EZH2 as a transcription repressor is well characterized. However, its role during vertebrate development is still poorly understood, particularly in neurogenesis. Here, we uncover the role of EZH2 in controlling the integrity of the neural tube and allowing proper progenitor proliferation. We demonstrate that knocking down the EZH2 in chick embryo neural tubes unexpectedly disrupts the neuroepithelium (NE) structure, correlating with alteration of the Rho pathway, and reduces neural progenitor proliferation. Moreover, we use transcriptional profiling and functional assays to show that EZH2-mediated repression of p21contributes to both processes. Accordingly, overexpression of cytoplasmic p21induces NE structural alterations and p21suppression rescues proliferation defects and partially compensates for the structural alterations and the Rho activity. Overall, our findings describe a new role of EZH2 in controlling the NE integrity in the neural tube to allow proper progenitor proliferation.