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.
Yang
Zhiyuan
Z
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Yik
Jasper H N
JH
Chen
Ruichuan
R
He
Nanhai
N
Jang
Moon Kyoo
MK
Ozato
Keiko
K
Zhou
Qiang
Q
D001483:Base Sequence; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics / Q000378:metabolism; D015696:Gene Products, tat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus; D000092468:Bromodomain Containing Proteins
D042863:Cyclin-Dependent Kinase 9; D015696:Gene Products, tat; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D042925:Positive Transcriptional Elongation Factor B; D012319:RNA Polymerase II; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; C486694:Brd4 protein, mouse; D000092468:Bromodomain Containing Proteins