Paper Info
Title
Chromatin Loops As Allosteric Modulators Of Enhancer-Promoter Interactions
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 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.
Year
DOI
Venue
2014
10.1371/journal.pcbi.1003867
PLOS COMPUTATIONAL BIOLOGY
Keywords
DocType
Volume
biomedical research,bioinformatics
Journal
10
Issue
ISSN
Citations 
10
1553-7358
5
PageRank 
References 
Authors
0.97
2
4
Name
Order
Citations
PageRank
Boryana Doyle150.97
Geoffrey Fudenberg261.34
Maxim Imakaev350.97
Leonid A. Mirny4698.99