Figure 2. Architectural proteins act combinatorially to organize chromatin at different length-scales.
A) TAD boundaries are enriched for CTCF and Cohesin, but these proteins can also act in combination with other factors, such as Mediator to partition these large Mb-scale TADs into smaller sub-TADs and to facilitate enhancer-promoter interactions.
B) A gene regulatory event involving a constitutive promoter-enhancer interaction. Pre-established Mediator-dependent looping of "anti-pause" enhancers to a target gene promoter is followed by the recruitment of the jumonji C-domain-containing protein 6 (JMJD6) and bromodomain-containing protein 4 (Brd4) complex. Brd4/JMJD6-dependent erasure of H4R3me2 and concomitant decapping/demethylation of 7SK snRNA ensures the release of the 7SK snRNA/HEXIM complex, which inhibits elongation factor P-TEFb, permitting pause release and transcriptional elongation.