Kostya I. Panov,
Jackie Russell, and
Joost C. B. M. Zomerdijk*
Division of Gene Regulation and Expression, Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
Received 18 April 2006/ Returned for modification 9 May 2006/ Accepted 1 June 2006
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 Iß isoform
and not with Pol I
. Chromatin immunoprecipitation analysis
places CK2 at the ribosomal DNA (rDNA) promoter in vivo. Pol
Iß-associated CK2 can phosphorylate topoisomerase II
in Pol Iß, 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.
These
authors contributed equally to this work.
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