Recruitment of P-TEFb for Stimulation of Transcriptional Elongation by the Bromodomain Protein Brd4

• Published in: Molecular cell Vol. 19; no. 4; pp. 535 - 545
• Main Authors: Yang, Zhiyuan, Yik, Jasper H.N., Chen, Ruichuan, He, Nanhai, Jang, Moon Kyoo, Ozato, Keiko, Zhou, Qiang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.08.2005
• Subjects: Base Sequence; Cyclin-Dependent Kinase 9 - genetics; Cyclin-Dependent Kinase 9 - metabolism; Gene Products, tat - genetics; HeLa Cells; HIV-1 - genetics; Humans; Molecular Sequence Data; Nuclear Proteins; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - metabolism; Positive Transcriptional Elongation Factor B - metabolism; RNA Polymerase II - metabolism; tat Gene Products, Human Immunodeficiency Virus; Transcription Factors; Transcription, Genetic
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2005.06.029

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.