Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/6584
Título
The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription and Cell Identity
Autor(es)
Lynch, Cian J | Bernad, Raquel | Calvo, Isabel | Nóbrega-Pereira, Sandrina | Ruiz, Sergio | Ibarz, Nuria | Martinez del Val, Ana CNIO | Graña Castro, Osvaldo CNIO | Gomez Lopez, Gonzalo CNIO | Andrés-León, Eduardo | Espinosa Angarica, Vladimir | Del Sol, Antonio | Ortega Jimenez, Sagrario CNIO | Fernandez-Capetillo, Oscar CNIO | Rojo, Enrique | Muoz Peralta, Javier CNIO | Serrano Marugan , Manuel CNIO
Fecha de publicación
2018-01-09
Cita
Cell Rep. 2018; 22(2): 396-410.
Idioma
Inglés
Tipo de documento
journal article
Resumen
The RNA polymerase II-associated protein 1 (RPAP1) is conserved across metazoa and required for stem cell differentiation in plants; however, very little is known about its mechanism of action or its role in mammalian cells. Here, we report that RPAP1 is essential for the expression of cell identity genes and for cell viability. Depletion of RPAP1 triggers cell de-differentiation, facilitates reprogramming toward pluripotency, and impairs differentiation. Mechanistically, we show that RPAP1 is essential for the interaction between RNA polymerase II (RNA Pol II) and Mediator, as well as for the recruitment of important regulators, such as the Mediator-specific RNA Pol II factor Gdown1 and the C-terminal domain (CTD) phosphatase RPAP2. In agreement, depletion of RPAP1 diminishes the loading of total and Ser5-phosphorylated RNA Pol II on many genes, with super-enhancer-driven genes among the most significantly downregulated. We conclude that Mediator/RPAP1/RNA Pol II is an ancient module, conserved from plants to mammals, critical for establishing and maintaining cell identity.
Palabras clave
Mediator | RNA polymerase II | Cell identity | Differentiation | Enhancer | Interactome | Transcription
Versión en línea
DOI
Aparece en las colecciones
Ficheros en el ítem
- Nombre:
- thernapolymerasefactor-mmc2.xlsx
- Tamaño:
- 3.704Mb
- Formato:
- Microsoft Excel 2007