Feb 26, 2014

Chromatin Loops as Allosteric Modulators of Enhancer-Promoter Interactions

BioRxiv : the Preprint Server for Biology
Boryana DoyleLeonid Mirny

Abstract

The 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 d...Continue Reading

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Mentioned in this Paper

Study
Chromatin Loop
Genome
Spatial Distribution
Genomic Stability
Macromolecular Alteration
Promoter
Protein kinase modulator
Gene Expression
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