title: Functional characterization of core promoter elements: DPE-specific transcription requires the protein kinase CK2 and the PC4 coactivator.
abstract: 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.
authors.affiliation: 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.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Lewis
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Sims
authors.forename: William S
authors.initials: WS
authors.lastname: Lane
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
mesh_terms: 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*
chemical_list: 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