Affiliation:
1. Division of Gene Regulation and Expression, Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
Abstract
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 Iβ isoform
and not with Pol Iα. Chromatin immunoprecipitation analysis
places CK2 at the ribosomal DNA (rDNA) promoter in vivo. Pol
Iβ-associated CK2 can phosphorylate topoisomerase IIα
in Pol Iβ, activator upstream binding factor (UBF), and
selectivity factor 1 (SL1) subunit TAF
I
110. 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 TAF
I
110,
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.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
56 articles.
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