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Genes & Dev. 17 (6): 748-758

Copyright © 2003 by Cold Spring Harbor Laboratory Press.

Vol. 17, No. 6, pp. 748-758, March 15, 2003

A model of repression: CTD analogs and PIE-1 inhibit transcriptional elongation by P-TEFb

Fan Zhang,1,4 Matjaz Barboric,1,2,4 T. Keith Blackwell,3 and B. Matija Peterlin1,5

1 Departments of Medicine, Microbiology and Immunology, Rosalind Russell Medical Research Center, University of California at San Francisco, San Francisco, California 94143, USA; 2 Institute of Biochemistry, Medical Faculty of the University of Ljubljana, Republic of Slovenia; 3 Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA

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.

[Keywords: P-TEFb; CTD; PIE-1; transcription; repression; elongation]

4 These authors contributed equally to this work.

5 Correponding author.

© 2003 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/03 $5.00

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