Enhancer-promoter pairs in the context of other interactions.

Experimental Studies, (A) Illustration of an enhancer (in yellow) spatially interacting with a promoter (blue) along a chromatin fiber. This coloring convention continues throughout the paper. (B) A recent study in Drosophila suggested a 7 kb chromatin loop formed between Su(Hw) insulators (orange) could decrease E-P interactions (red “X”) [20]. (C) Conversely, a 3 kb chromatin loop in the region between enhancer and promoter was proposed to increase E-P interactions. (D) Five arrangements for proposed looping interactions from three studies, left to right, [21], [22], and [23]. (left) a single Drosophila gypsy element between an enhancer and a promoter did not change their interactions (top), however an additional gypsy element upstream of the enhancer decreased E-P interactions (bottom) [21]. (center) at the mouse H19 locus, a regulatory element with multiple larger loops (55 kb and 25 kb) was suggested to control multiple E-P contacts; the enhancer can regulate the promoter before the loop, but cannot regulate the promoter within the loop [22]. (right) chromatin loops may also modulate spatial interactions between silencing elements (e.g. PRE, black triangles) and their target promoters [23]. The promoter within the loop is not silenced (top), whereas the promoter beyond the loop is silenced (bottom). Polymer Simulations, (E) Arrangement 1: polymer conformation where an enhancer is within a chromatin loop and a promoter is beyond the loop. (F) Arrangement 2: polymer conformation where an enhancer is before the loop and a promoter is after the loop. (G) (left) zoom-in on our polymer model of chromatin. The three large circles represent one monomer each; each monomer consists of three nucleosomes (small circles) or 500 bp. (right) full view of a sample polymer conformation showing a 30 kb chromatin loop (black) with highlighted loop-bases (orange) within a 1 Mb region.