Fig. 1

Comparison of typical enhancers and SEs. SEs are enriched with more TFs, HMEs(EP300 and HDAC), and SE-cofactors (BET family proteins, mediator complexes, and CDKs), than typical enhancers. Thus, SEs have stronger regulatory functions than typical enhancers. Furthermore, SE regions bind SE complexes in an order. First, histone acetylating transferases such as p300/CBP are recruited by TFs, promoting nonhistone protein and nucleosome acetylation. Second, BET proteins interact with hyperacetylated histone sites across chromatin, establishing transcriptionally active regulatory regions because of their increased affinity for proteins with many acetylated residues. The establishment of synergistic high-density and cooperative transcriptional complexes at SEs is facilitated by BRD4 and mediator complexes, thereby altering the chromatin structure, dynamics, and function. Finally, a P-TEFb complex and CDK7 work in concert to release RNA Pol II and activate transcription. (BRDs = Bromine domain proteins, CDKs = Cyclin-dependent kinases, HDAC = Histone deacetylase, HMEs = Histone modifying enzymes, H3K27ac = Histone H3 lysine 27 acetylation; H3K4me1 = Histone H3 lysine 4 mono-methylation; P-TEFb = positive transcription elongation factor-b; TF = Transcription factor.)