[PDF][PDF] The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription

MK Jang, K Mochizuki, M Zhou, HS Jeong, JN Brady… - Molecular cell, 2005 - cell.com
MK Jang, K Mochizuki, M Zhou, HS Jeong, JN Brady, K Ozato
Molecular cell, 2005cell.com
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 …
Summary
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.
cell.com