title: Casein kinase 2 associates with initiation-competent RNA polymerase I and has multiple roles in ribosomal DNA transcription.
abstract: Mammalian RNA polymerase I (Pol I) complexes contain a number of associated factors, some with undefined regulatory roles in transcription. We demonstrate that casein kinase 2 (CK2) in human cells is associated specifically only with the initiation-competent Pol Ibeta isoform and not with Pol Ialpha. Chromatin immunoprecipitation analysis places CK2 at the ribosomal DNA (rDNA) promoter in vivo. Pol Ibeta-associated CK2 can phosphorylate topoisomerase IIalpha in Pol Ibeta, activator upstream binding factor (UBF), and selectivity factor 1 (SL1) subunit TAFI110. A potent and selective CK2 inhibitor, 3,8-dibromo-7-hydroxy-4-methylchromen-2-one, limits in vitro transcription to a single round, suggesting a role for CK2 in reinitiation. Phosphorylation of UBF by CK2 increases SL1-dependent stabilization of UBF at the rDNA promoter, providing a molecular mechanism for the stimulatory effect of CK2 on UBF activation of transcription. These positive effects of CK2 in Pol I transcription contrast to that wrought by CK2 phosphorylation of TAFI110, which prevents SL1 binding to rDNA, thereby abrogating the ability of SL1 to nucleate preinitiation complex (PIC) formation. Thus, CK2 has the potential to regulate Pol I transcription at multiple levels, in PIC formation, activation, and reinitiation of transcription.
authors.affiliation: Division of Gene Regulation and Expression, School of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, United Kingdom.
authors.forename: Tatiana B
authors.initials: TB
authors.lastname: Panova
authors.forename: Kostya I
authors.initials: KI
authors.lastname: Panov
authors.forename: Jackie
authors.initials: J
authors.lastname: Russell
authors.forename: Joost C B M
authors.initials: JC
authors.lastname: Zomerdijk
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D021122:Protein Subunits; D035362:Transcription Factor TFIID; C063844:transcription factor UBF; D010770:Phosphotransferases; D047390:Casein Kinase II; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D004250:DNA Topoisomerases, Type II