Figure 2. Model incorporating BRD4 molecular functions and the proposed sequence in which its enzymatic activities function.

BRD4 binds to mitotic chromatin, bookmarking early G1 genes. Toward the end of mitosis, BRD4 acetylates histones, initially on the tail lysines and eventually on H3K122 in the globular region of histone H3, which leads to nucleosome clearance and enables the recruitment of transcription machinery. BRD4 then regulates transcriptional pause release and elongation via its phosphorylation of RNA Pol II CTD and its recruitment of PTEFb to the preinitiation complex containing transcription factor II H (TFIIH).