Functional characterization of core promoter elements: DPE-specific transcription requires the protein kinase CK2 and the PC4 coactivator.
Downstream core promoter elements are an expanding class of regulatory sequences that add considerable diversity to the promoter architecture of RNA polymerase II-transcribed genes. We set out to determine the factors necessary for downstream promoter element (DPE)-dependent transcription and find that, against expectations, TFIID and the GTFs are not sufficient. Instead, the protein kinase CK2 and the coactivator PC4 establish DPE-specific transcription in an in vitro transcription system containing TFIID, Mediator, and the GTFs. Chromatin immunoprecipitation analyses using the DPE-dependent IRF-1 and TAF7 promoters demonstrated that CK2, and PC4 are present on these promoters in vivo. In contrast, neither PC4 nor CK2 were detected on the TAF1-dependent cyclin D promoter, which contains a DCE type of downstream element. Our findings also demonstrate that CK2 activity alters TFIID-dependent recognition of DCE sequences. These data establish that CK2 acts as a switch, converting the transcriptional machinery from functioning on one type of downstream element to another.
Lewis
Brian A
BA
Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Sims
Robert J
RJ
Lane
William S
WS
Reinberg
Danny
D
D047390:Casein Kinase II / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins; D050856:Interferon Regulatory Factor-1; D008565:Membrane Proteins; D010750:Phosphoproteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D035362:Transcription Factor TFIID / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
D004268:DNA-Binding Proteins; C490043:IFRD2 protein, human; C494257:IRF1 protein, human; D017874:Immediate-Early Proteins; D050856:Interferon Regulatory Factor-1; D008565:Membrane Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; C091537:TAF7 protein, human; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators; D035362:Transcription Factor TFIID; D047390:Casein Kinase II