title: Competition with TATA box-binding protein for binding to the TATA box implicated in human cytomegalovirus IE2-mediated transcriptional repression of cellular promoters.
abstract: The human cytomegalovirus IE2 is a sequence-specific DNA-binding protein. A consensus IE2-binding site (IBS) contains two copies of the dinucleotide CG separated by 10 not well-conserved but AT-rich nucleotides. In this report, we demonstrated that the TATA box of the insulin-like growth factor binding protein 4 (IGFBP4) promoter is embedded in an IBS. In a transient transfection study, IE2-mediated repression of a reporter driven either by a synthetic promoter containing the IGFBP4 TATA/IBS element or by the native IGFBP4 promoter was dependent on the intactness of the IBS. Competition with TBP for binding to the IGFBP4 TATA/IBS element may underlie the mechanism for the IE2-mediated repression, because IE2 and TATA box-binding protein (TBP) binding to the IGFBP4 TATA/IBS element are mutually elusive. Moreover, the TATA boxes of several other genes, including ADA and CPH-70, are likewise confined in IBS-like sequences. The IE2 interacts with those TATA/IBS elements in vitro and inhibits transcription driven by them in vivo, supporting the idea that competitive inhibition of TBP binding to the TATA box represents a novel mechanism exploited by IE2 to repress cellular gene expression.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Y C
authors.initials: YC
authors.lastname: Wang
authors.forename: C F
authors.initials: CF
authors.lastname: Huang
authors.forename: S F
authors.initials: SF
authors.lastname: Tung
authors.forename: Y S
authors.initials: YS
authors.lastname: Lin
mesh_terms: D001665:Binding Sites; D001667:Binding, Competitive; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016385:TATA Box; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins; D014764:Viral Proteins
chemical_list: D004268:DNA-Binding Proteins; C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D018974:Insulin-Like Growth Factor Binding Protein 4; D008562:Membrane Glycoproteins; D009841:Oligonucleotides; D011993:Recombinant Fusion Proteins; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D014157:Transcription Factors; C077406:UL115 protein, Human herpesvirus 5; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; C439068:glycoprotein O, cytomegalovirus; D015500:Chloramphenicol O-Acetyltransferase