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Chromatin-wide profiling of DYRK1A reveals a role as a gene-specific RNA polymerase II CTD kinase

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dc.contributor.author Vona, Chiara Di
dc.contributor.author Bezdan, Daniela
dc.contributor.author Islam, Abul, 1978-
dc.contributor.author Salichs Fradera, Eulàlia
dc.contributor.author López Bigas, Núria
dc.contributor.author Ossowski, Stephan
dc.contributor.author Luna, Susana de la
dc.date.accessioned 2016-02-11T15:29:33Z
dc.date.available 2016-02-11T15:29:33Z
dc.date.issued 2015
dc.identifier.citation Di 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.2014.12.026
dc.identifier.issn 1097-2765
dc.identifier.uri http://hdl.handle.net/10230/25792
dc.description.abstract DYRK1A 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.
dc.description.sponsorship This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO: BFU2010-15347, BFU2013-44513 to S.d.l.L., SAF2012-36199 to N.L.-B., and ‘Centro de Excelencia Severo Ochoa 2013-2017’-SEV-2012-0208) and the Secretariat of Universities and Research-Government of Catalonia (2014SGR674 to S.d.l.L.). C.D.V. and E.S. were FPI predoctoral fellows financed by MINECO (BES2008-002751 and BES2005-10136)
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Molecular Cell. 2015;57(3):506-20
dc.rights © 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-license
dc.subject.other Proteïnes quinases -- Metabolisme
dc.subject.other RNA missatger
dc.title Chromatin-wide profiling of DYRK1A reveals a role as a gene-specific RNA polymerase II CTD kinase
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.molcel.2014.12.026
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2010-15347
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2013-44513
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-36199
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SEV-2012-0208
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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