The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription and Cell Identity

• DOI: 10.1016/j.celrep.2017.12.062
• Publication Date: 2018-01-09T16:44:13Z
• Authors: Cian J. Lynch; Raquel Bernad; Isabel Calvo; Sandrina Nóbrega-...; Sergio Ruiz; Nuria Ibarz; Ana Martinez-Val; Osvaldo Graña-Castro; Gonzalo Gómez-López; Eduardo Andrés-León; Vladimir Espinosa...; Antonio del Sol; Sagrario Ortega; Oscar Fernandez-C...; Enrique Rojo; Javier Munoz; Manuel Serrano
• Keywords: RNA polymerase II; Mediator; RNA polymerase I; RNA polymerase III

The RNA polymerase II-associated protein 1 (RPAP1) is conserved across metazoa and required for stem cell differentiation in plants; however, very little known about its mechanism of action or role mammalian cells. Here, we report that RPAP1 essential the expression identity genes viability. Depletion triggers de-differentiation, facilitates reprogramming toward pluripotency, impairs differentiation. Mechanistically, show interaction between II (RNA Pol II) Mediator, as well recruitment important regulators, such Mediator-specific factor Gdown1 C-terminal domain (CTD) phosphatase RPAP2. In agreement, depletion diminishes loading total Ser5-phosphorylated on many genes, with super-enhancer-driven among most significantly downregulated. We conclude Mediator/RPAP1/RNA an ancient module, from plants to mammals, critical establishing maintaining identity.