Enhancer-promoter communication at theDrosophila engrailedlocus

Abstract

Enhancers are often located many tens of kilobases away from the promoter they regulate, sometimes residing closer to the promoter of a neighboring gene. How do they know which gene to activate? We have used homing P[en]constructs to study the enhancer-promoter communication at the engrailed locus. Here we show that engrailed enhancers can act over large distances, even skipping over other transcription units,choosing the engrailed promoter over those of neighboring genes. This specificity is achieved in at least three ways. First, early acting engrailed stripe enhancers exhibit promoter specificity. Second, a proximal promoter-tethering element is required for the action of the imaginal disc enhancer(s). Our data suggest that there are two partially redundant promoter-tethering elements. Third, the long-distance action of engrailed enhancers requires a combination of the engrailedpromoter and sequences within or closely linked to the promoter proximal Polycomb-group response elements. These data show that multiple mechanisms ensure proper enhancer-promoter communication at the Drosophila engrailed locus.

Enhancer trap infidelity inDrosophila optomotor-blind

“…[46][47][48] Core promoter (TATA and DPE) and promoter proximal elements have been demonstrated in several cases to govern specificity in enhancerpromoter communication. [49][50][51] We reasoned that a defect in the pGawB Gal4 promoter region could account for the restricted reporting activity of ombP4 (compare ref. 46).…”

“…63,64 and Drosophila genes. 51,[65][66][67][68][69][70] In the proximity hypothesis we posit that (1) pGawB but not PlacW or PGalW require proximity to promoter proximal elements in order to report the full spectrum of enhancer activity and that (2) omb P3 inserted at around 1.5 kb upstream of exon I does profit from such elements whereas omb P4 inserted 12 kb downstream of exon I and 2 kb upstream of exon Ia does not.…”

Quantitation of interactions between two DNA loops demonstrates loop domain insulation in E. coli cells

“…Chromatin capture studies show that enhancers and promoters are connected in highly complex condition-dependent patterns (6,15,17). Although core enhancer and promoter elements can provide some specificity (18), enhancers are often able to activate heterologous promoters if they are placed near to each other. Indeed, this lack of specificity is the basis for standard enhancer assays and screens (7,14,19).…”

“…1A), because the efficiency of contact increases as the length of the DNA tether between the sites shortens (20)(21)(22)(23)(24). Promoter-tethering elements in Drosophila that allow activation by specific enhancers over long distances are proposed to form DNA loops between sequences near the enhancer and the promoter (18,25). In the mouse β-globin locus, the Ldb1 protein binds to proteins at the locus control region and at the promoter and appears to form a bridge necessary for efficient enhancer-promoter contact (26).…”

Comparing Enhancer Action in Cis and in Trans

“…Some examples of transvection at the Abdominal-B locus require a 10-kb sequence dubbed the transvection-mediating region (tmr) (Hopmann et al 1995), and transgenic studies have shown that the tmr can positively affect pairing (Ronshaugen and Levine 2004). Similarly, long-distance interactions between enhancers and promoters in cis can be facilitated by promoter tethering sequences (Zhou and Levine 1999;Calhoun et al 2002;Calhoun and Levine 2003;Lin 2003;Akbari et al 2008;Fujioka et al 2009;Kwon et al 2009). It is as yet unclear whether similar sequences are required for any enhancer to act in trans or, alternatively, whether transvection between regulatory elements is a natural consequence once chromosomes are physically paired.…”