Brd2 is a TBP-associated protein and recruits TBP into E2F-1 transcriptional complex in response to serum stimulation.
Brd2 is a novel protein kinase and plays a role in cell cycle-responsive transcription. Recent studies show that Brd2 contributes to E2F-1 regulated cell cycle progression. In this process, Brd2 exhibits scaffold or transcriptional adapter functions and mediates recruitment of both E2F-1 transcription factors and chromatin-remodelling activity to the E2F-1-resposive promoter. In the present study, we show that Brd2 is also a TBP-associated protein and a 26 amino acids peptide in the first bromodomain of Brd2 is essential for Brd2-TBP interaction. We found that serum stimulation of serum starved NIH/3T3 cells efficiently induces the formation of the Brd2-E2F-1-TBP complex in vivo. In this process, Brd2 plays a pivotal role in the recruitment of TBP into a E2F-1 transcriptional complex, as tested in overexpression assay and at the endogenous level. Furthermore, the 26 amino acid peptide that mediates Brd2-TBP interaction is proved to be critical for Brd2-dependent transactivation on E2F-1-responsive promoters, and moreover, Brd2 and E2F-1 may cooperatively participate in various serum-induced transactivation processes in Luciferase-reporter assays. Thus taken together, because Brd2 may recruit a HAT in its transactivational complex and E2F-1 has been found to stimulate transcription by recruiting acetyltransferase and cofactors GCN5, we predict that Brd2 and E2F-1 may act in a cooperative way to introduce an optimal environment for TBP binding to the TATA-element of gene promoters.
Peng
Jinhong
J
National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei, People's Republic of China.
Dong
Wei
W
Chen
Lu
L
Zou
Tingting
T
Qi
Yipeng
Y
Liu
Yingle
Y
D000818:Animals; D002868:Chromosomal Proteins, Non-Histone; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D017353:Gene Deletion; D015151:Immunoblotting; D051379:Mice; D041681:NIH 3T3 Cells; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D044967:Serum; D035181:TATA-Box Binding Protein / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection; D014170:Transformation, Genetic; D000092468:Bromodomain Containing Proteins
D002868:Chromosomal Proteins, Non-Histone; D050687:E2F1 Transcription Factor; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; C490844:Brd2 protein, mouse; D000092468:Bromodomain Containing Proteins