Chromatin Loops as Allosteric Modulators of Enhancer-Promoter Interactions

BioRxiv : the Preprint Server for Biology
Boryana DoyleLeonid A 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

Related Concepts

Allosteric Regulation
Chromatin
Gene Expression
Microscopy
Polymers
Regulatory Sequences, Nucleic Acid
Spatial Distribution
Protein kinase modulator
Promoter
Proximal

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