title: The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription.
abstract: Brd4 is a mammalian bromodomain protein that binds to acetylated chromatin. Proteomic analysis revealed that Brd4 interacts with cyclinT1 and Cdk9 that constitutes core positive transcription elongation factor b (P-TEFb). Brd4 interacted with P-TEFb in the living nucleus through its bromodomain. About half of P-TEFb was bound to the inhibitory subunit and functionally inactive. Brd4 interacted with P-TEFb that was free of the inhibitory subunit. An increase in Brd4 expression led to increased P-TEFb-dependent phosphorylation of RNA polymerase II (RNAPII) CTD and stimulation of transcription from promoters in vivo. Conversely, a reduction in Brd4 expression by siRNA reduced CTD phosphorylation and transcription, revealing that Brd4 is a positive regulatory component of P-TEFb. In chromatin immunoprecipitation (ChIP) assays, the recruitment of P-TEFb to a promoter was dependent on Brd4 and was enhanced by an increase in chromatin acetylation. Together, P-TEFb alternately interacts with Brd4 and the inhibitory subunit to maintain functional equilibrium in the cell.
authors.affiliation: Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Moon Kyoo
authors.initials: MK
authors.lastname: Jang
authors.forename: Kazuki
authors.initials: K
authors.lastname: Mochizuki
authors.forename: Meisheng
authors.initials: M
authors.lastname: Zhou
authors.forename: Ho-Sang
authors.initials: HS
authors.lastname: Jeong
authors.forename: John N
authors.initials: JN
authors.lastname: Brady
authors.forename: Keiko
authors.initials: K
authors.lastname: Ozato
mesh_terms: D000818:Animals; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology*; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000502:physiology*; D000092468:Bromodomain Containing Proteins
chemical_list: D042863:Cyclin-Dependent Kinase 9; D018076:DNA, Complementary; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D042925:Positive Transcriptional Elongation Factor B; D012319:RNA Polymerase II; D012342:RNA, Small Nuclear; D014157:Transcription Factors; C486694:Brd4 protein, mouse; D000092468:Bromodomain Containing Proteins; C467972:Cdk9 protein, mouse