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oai:repisalud.isciii.es:20.500.12105/65842024-11-30T00:23:13Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Lynch, Cian J author Bernad, Raquel author Calvo, Isabel author Nóbrega-Pereira, Sandrina author Ruiz, Sergio author Ibarz, Nuria author Martinez del Val, Ana author Graña Castro, Osvaldo author Gomez Lopez, Gonzalo author Andrés-León, Eduardo author Espinosa Angarica, Vladimir author Del Sol, Antonio author Ortega Jimenez, Sagrario author Fernandez-Capetillo, Oscar author Rojo, Enrique author Muoz Peralta, Javier author Serrano Marugan , Manuel author 2018-01-09 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. Cell Rep. 2018; 22(2): 396-410. 10.1016/j.celrep.2017.12.062 2211-1247 22111247 Cell reports 29320736 http://hdl.handle.net/20.500.12105/6584 Mediator RNA polymerase II Cell identity Differentiation Enhancer Interactome Transcription The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription and Cell Identity