Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4.

The cyclinT1/Cdk9 heterodimer that constitutes core P-TEFb is generally presumed to be the transcriptionally active form for stimulating RNA polymerase II elongation. About half of cellular P-TEFb also exists in an inactive complex with the 7SK snRNA and the HEXIM1 protein. Here, we show that the remaining half associates with ...
the bromodomain protein Brd4. In stress-induced cells, the 7SK/HEXIM1-bound P-TEFb is quantitatively converted into the Brd4-associated form. The association with Brd4 is necessary to form the transcriptionally active P-TEFb, recruits P-TEFb to a promoter, and enables P-TEFb to contact the Mediator complex, a potential target for the Brd4-mediated recruitment. Although generally required for transcription, the P-TEFb-recruitment function of Brd4 can be substituted by that of HIV-1 Tat, which recruits P-TEFb directly for activated HIV-1 transcription. Brd4, HEXIM1, and 7SK are all implicated in regulating cell growth, which may result from their dynamic control of the general transcription factor P-TEFb.
Mesh Terms:
Base Sequence, Cyclin-Dependent Kinase 9, Gene Products, tat, HIV-1, HeLa Cells, Humans, Molecular Sequence Data, Nuclear Proteins, Oncogene Proteins, Fusion, Positive Transcriptional Elongation Factor B, RNA Polymerase II, Transcription Factors, Transcription, Genetic, tat Gene Products, Human Immunodeficiency Virus
Mol. Cell
Date: Aug. 19, 2005
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