Doyle, BoryanaFudenberg, GeoffreyImakaev, MaximMirny, Leonid2014-11-032014Doyle, Boryana, Geoffrey Fudenberg, Maxim Imakaev, and Leonid A. Mirny. 2014. “Chromatin Loops as Allosteric Modulators of Enhancer-Promoter Interactions.” PLoS Computational Biology 10 (10): e1003867. doi:10.1371/journal.pcbi.1003867. http://dx.doi.org/10.1371/journal.pcbi.1003867.1553-734Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13347404The classic model of eukaryotic gene expression requires direct spatial contact between a distal enhancer and a proximal promoter. Recent Chromosome Conformation Capture (3C) studies show that enhancers and promoters are embedded in a complex network of looping interactions. Here we use a polymer model of chromatin fiber to investigate whether, and to what extent, looping interactions between elements in the vicinity of an enhancer-promoter pair can influence their contact frequency. Our equilibrium polymer simulations show that a chromatin loop, formed by elements flanking either an enhancer or a promoter, suppresses enhancer-promoter interactions, working as an insulator. A loop formed by elements located in the region between an enhancer and a promoter, on the contrary, facilitates their interactions. We find that different mechanisms underlie insulation and facilitation; insulation occurs due to steric exclusion by the loop, and is a global effect, while facilitation occurs due to an effective shortening of the enhancer-promoter genomic distance, and is a local effect. Consistently, we find that these effects manifest quite differently for in silico 3C and microscopy. Our results show that looping interactions that do not directly involve an enhancer-promoter pair can nevertheless significantly modulate their interactions. This phenomenon is analogous to allosteric regulation in proteins, where a conformational change triggered by binding of a regulatory molecule to one site affects the state of another site.en-USBiology and Life SciencesBiophysicsGeneticsGene ExpressionGene RegulationEnhancer ElementsJournal Article2014-11-0310.1371/journal.pcbi.1003867