Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/8360
Título
ERF deletion rescues RAS deficiency in mouse embryonic stem cells
Autor(es)
Mayor-Ruiz, Cristina CNIO | Olbrich, Teresa | Drosten, Matthias CNIO | Lecona, Emilio | Vega-Sendino, Maria | Ortega Jimenez, Sagrario CNIO | Dominguez, Orlando CNIO | Barbacid, Mariano CNIO | Ruiz, Sergio | Fernandez-Capetillo, Oscar CNIO
Fecha de publicación
2018-04-01
Cita
Genes Dev. 2018;32(7-8):568-576
Idioma
Inglés
Tipo de documento
journal article
Resumen
MEK inhibition in combination with a glycogen synthase kinase-3β (GSK3β) inhibitor, referred as the 2i condition, favors pluripotency in embryonic stem cells (ESCs). However, the mechanisms by which the 2i condition limits ESC differentiation and whether RAS proteins are involved in this phenomenon remain poorly understood. Here we show that RAS nullyzygosity reduces the growth of mouse ESCs (mESCs) and prohibits their differentiation. Upon RAS deficiency or MEK inhibition, ERF (E twenty-six 2 [Ets2]-repressive factor), a transcriptional repressor from the ETS domain family, translocates to the nucleus, where it binds to the enhancers of pluripotency factors and key RAS targets. Remarkably, deletion of Erf rescues the proliferative defects of RAS-devoid mESCs and restores their capacity to differentiate. Furthermore, we show that Erf loss enables the development of RAS nullyzygous teratomas. In summary, this work reveals an essential role for RAS proteins in pluripotency and identifies ERF as a key mediator of the response to RAS/MEK/ERK inhibition in mESCs.
Palabras clave
MESH
Animals | Cell Differentiation | Cell Line | Embryonic Stem Cells | Enhancer Elements, Genetic | Gene Deletion | Mice | Mice, Nude | Repressor Proteins | Teratoma | Genes, ras
Versión en línea
DOI
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