Títol:
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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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Autor/a:
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Vona, Chiara Di; Bezdan, Daniela; Islam, Abul, 1978-; Salichs Fradera, Eulàlia; López Bigas, Núria; Ossowski, Stephan; Luna, Susana de la
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Abstract:
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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. |
Abstract:
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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) |
Matèries:
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-Proteïnes quinases -- Metabolisme -RNA missatger |
Drets:
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© 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 |
Tipus de document:
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Article Article - Versió publicada |
Publicat per:
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Elsevier
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