[PDF][PDF] Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4

Z Yang, JHN Yik, R Chen, N He, MK Jang, K Ozato… - Molecular cell, 2005 - cell.com
Z Yang, JHN Yik, R Chen, N He, MK Jang, K Ozato, Q Zhou
Molecular cell, 2005cell.com
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 …
Summary
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.
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