2026-06-14T06:44:16Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65842024-11-30T00:23:13Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Botín Foundation
funder
Fundación Ramón Areces
funder
Fundación AXA
funder
Ministerio de Economía y Competitividad (España)
2018-11-14T09:42:15Z
2018-11-14T09:42:15Z
2018-01-09
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
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.
eng
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
journal article
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