title: A model of repression: CTD analogs and PIE-1 inhibit transcriptional elongation by P-TEFb.
abstract: The positive transcription elongation factor b (P-TEFb) contains cyclin T1 (CycT1) and cyclin-dependent kinase 9 (Cdk9). For activating the expression of eukaryotic genes, the histidine-rich sequence in CycT1 binds the heptapeptide repeats in the C-terminal domain (CTD) of RNA polymerase II (RNAPII), whereupon Cdk9 phosphorylates the CTD. We found that alanine-substituted heptapeptide repeats that cannot be phosphorylated also bind CycT1. When placed near transcription units, these CTD analogs block effects of P-TEFb. Remarkably, the transcriptional repressor PIE-1 from Caenorhabditis elegans behaves analogously. It binds CycT1 via an alanine-containing heptapeptide repeat and inhibits transcriptional elongation. Thus, our findings reveal a new mechanism by which repressors inhibit eukaryotic transcription.
authors.affiliation: Departments of Medicine, Microbiology and Immunology, Rosalind Russell Medical Research Center, University of California at San Francisco, San Francisco, CA 94143, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Matjaz
authors.initials: M
authors.lastname: Barboric
authors.forename: T Keith
authors.initials: TK
authors.lastname: Blackwell
authors.forename: B Matija
authors.initials: BM
authors.lastname: Peterlin
mesh_terms: D000409:Alanine / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D015153:Blotting, Western; D019556:COS Cells; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D018698:Glutamic Acid / Q000737:chemistry; D006367:HeLa Cells; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D042925:Positive Transcriptional Elongation Factor B; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry* / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D029742:Caenorhabditis elegans Proteins; D009687:Nuclear Proteins; D010455:Peptides; C100950:pie-1 protein, C elegans; D018698:Glutamic Acid; D012694:Serine; D006639:Histidine; D042925:Positive Transcriptional Elongation Factor B; D017346:Protein Serine-Threonine Kinases; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases; C467968:cdk9 protein kinase, C elegans; D012319:RNA Polymerase II; D012260:Ribonucleases; D000409:Alanine