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Mol Cell. 2015 Feb 5;57(3):506-20. doi: 10.1016/j.molcel.2014.12.026. Epub 2015 Jan 22.

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

Author information

1
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.
2
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.
3
Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain; Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka 1000, Bangladesh.
4
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.
5
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.

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.

PMID:
25620562
DOI:
10.1016/j.molcel.2014.12.026
[Indexed for MEDLINE]
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