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The RNA Polymerase II factor RPAP1 is critical for Mediator-driven transcription and cell identity.

AuthorsLynch, C.H.; Bernad, Raquel; Calvo, Isabel; Nóbrega-Pereira, Sandrina; Ruiz, Sergio; Ibarz, Nuria; Martínez del Val, Nuria; Graña, Osvaldo; Gómez-López, Gonzalo; Andrés-León, Eduardo; Espinosa Angarica, Vladimir; Sol, Antonio del; Ortega, Sagrario; Fernandez-Capetillo, Oscoar; Rojo, Enrique; Muñoz, Javier ; Serrano, Manuel
RNA polymerase II
Cell identity
Issue DateJan-2018
PublisherCell Press
CitationCell Reports 22 (2): 396-410 (2018)
AbstractThe 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.
Publisher version (URL)http://dx.doi.org/10.1016/j.celrep.2017.12.062
Appears in Collections:(CNB) Artículos
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