Brd2 is a TBP-associated protein and recruits TBP into E2F-1 transcriptional complex in response to serum stimulation

Abstract

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.

Discovery and Characterization of Super-Enhancer-Associated Dependencies in Diffuse Large B Cell Lymphoma

“…Epigenomic analyses confirmed the co-localization of BRD4 and E2F1 at active promoters. The selective decrease in BRD4 loading of E2F1-driven genes following JQ1 treatment is consistent with studies suggesting a role of BET proteins in E2F1-mediated transcription (Peng et al, 2007; Sinha et al, 2005). Genome-wide assessment of effects of BRD4 on transcriptional elongation at E2F1 target genes were statistically significant but subtle on an individual gene level (data not shown), leaving open the possibility that BRD4-mediated effects on elongation are most apparent on super-enhancer associated genes.…”

Bromo- and Extraterminal Domain Chromatin Regulators Serve as Cofactors for Murine Leukemia Virus Integration

“…BRD2 localizes throughout the cell in resting cells, whereas mitogen treatment induces its nuclear localization (40). BRD2, and likely other BET proteins, acts as a scaffold on chromatin to recruit E2F proteins, histone deacetylases (HDACs), histone H4-specific acetyltransferase (HAT), and proteins involved in chromatin remodeling (41)(42)(43). BET proteins bind to acetylated histone tails via their bromodomains (44,45).…”

H2A.Z.1 Monoubiquitylation Antagonizes BRD2 to Maintain Poised Chromatin in ESCs

“…In vitro , Brd2 directly promotes transcription on a chromatinized template by acting as a chromatin remodeler (Leroy et al, 2008). Additionally, Brd2 can bind both TBP and Mediator, both of which are normally absent from bivalent promoters (Peng et al, 2006; Pinz et al, 2015). Thus, future studies will be directed toward understanding how H2A.Z.1ub inhibits gene activation through antagonism of Brd2.…”