title: Chromatin-wide profiling of DYRK1A reveals a role as a gene-specific RNA polymerase II CTD kinase.
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.
authors.affiliation: Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Spain.
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Vona
authors.affiliation: Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain; Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bezdan
authors.affiliation: Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain; Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka 1000, Bangladesh.
authors.forename: Abul B M M K
authors.initials: AB
authors.lastname: Islam
authors.affiliation: Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Spain.
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Salichs
authors.affiliation: Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, 08010 Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: López-Bigas
authors.affiliation: Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain; Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ossowski
authors.affiliation: Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, 08010 Barcelona, Spain. Electronic address: susana.luna@crg.eu.
authors.forename: Susana
authors.initials: S
authors.lastname: de la Luna
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D055029:Inverted Repeat Sequences; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II; D012333:RNA, Messenger / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014158:Transcription, Genetic; D000097603:Dyrk Kinases
chemical_list: D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D012319:RNA Polymerase II; D012333:RNA, Messenger; D012694:Serine; D000097603:Dyrk Kinases; C060137:carboxy-terminal domain kinase