Vona, Chiara DiBezdan, DanielaIslam, Abul, 1978-Salichs Fradera, EulàliaLópez Bigas, NúriaOssowski, StephanLuna, Susana de la2016-02-112016-02-112015Di Vona C, Bezdan D, Islam AB, Salichs E, López-Bigas N, Ossowski S et al. Chromatin-wide profiling of DYRK1A reveals a role as a gene-specific RNA polymerase II CTD kinase. Molecular Cell. 2015;57(3): 506-20. DOI: 10.1016/j.molcel.2014.12.0261097-2765http://hdl.handle.net/10230/25792DYRK1A is a dosage-sensitive protein kinase that fulfills key roles during development and in tissue homeostasis, and its dysregulation results in human pathologies. DYRK1A is present in both the nucleus and cytoplasm of mammalian cells, although its nuclear function remains unclear. Genome-wide analysis of DYRK1A-associated loci reveals that the kinase is recruited preferentially to promoters of genes actively transcribed by RNA polymerase II (RNAPII), which are functionally associated with translation, RNA processing, and cell cycle. DYRK1A-bound promoter sequences are highly enriched in a conserved palindromic motif, which is necessary to drive DYRK1A-dependent transcriptional activation. DYRK1A phosphorylates the C-terminal domain (CTD) of RNAPII at Ser2 and Ser5. Depletion of DYRK1A results in reduced association of RNAPII at the target promoters as well as hypophosphorylation of the RNAPII CTD along the target gene bodies. These results are consistent with DYRK1A being a transcriptional regulator by acting as a CTD kinase.application/pdfeng© Elsevier. This is the published version of an article http://dx.doi.org/10.1016/j.molcel.2014.12.026 that appeared in the journal Molecular Cell. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: http://www.elsevier.com/about/open-access/open-access-policies/oa-license-policy/elsevier-user-licenseProteïnes quinases -- MetabolismeRNA missatgerChromatin-wide profiling of DYRK1A reveals a role as a gene-specific RNA polymerase II CTD kinaseinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.molcel.2014.12.026info:eu-repo/semantics/openAccess