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Chromatin loops as modulators of enhancer-promoter interactions in their vicinity

Boryana Doyle, Geoffrey Fudenberg, Maxim Imakaev, Leonid A. Mirny
doi: https://doi.org/10.1101/003087
Boryana Doyle
1Program for Research in Mathematics, Engineering and Science for High School Students, PRIMES, Massachusetts Institute of Technology
2MIT Undergraduate Research Opportunities Program (UROP)
3Department of Physics, Massachusetts Institute of Technology
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Geoffrey Fudenberg
4Graduate Program in Biophysics, Harvard University
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Maxim Imakaev
3Department of Physics, Massachusetts Institute of Technology
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Leonid A. Mirny
3Department of Physics, Massachusetts Institute of Technology
4Graduate Program in Biophysics, Harvard University
5Institute for Medical Engineering and Science, Massachusetts Institute of Technology
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  • For correspondence: leonid@mit.edu
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Abstract

The classic model of eukaryotic gene expression requires direct spatial contact between a distal enhancer and a proximal promoter. However, recent chromosome conformation capture studies (e.g. Hi-C) show that enhancer and promoters are embedded in a complex network of cell-type specific looping interactions. Here we investigate whether, and to what extent, looping interactions between elements in the vicinity of an enhancer-promoter pair can influence the frequency of enhancer-promoter contacts. Our polymer simulations show that a chromatin loop formed by elements flanking either an enhancer or a promoter suppresses enhancer-promoter interactions, working as a topological 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 these two consequences of chromatin loops have different genomic extents, with facilitation being a local effect and insulation persisting over a large range of genomic distances. Overall, our results show that looping interactions which do not directly involve an enhancer-promoter contact can nevertheless significantly modulate their interactions. This illustrates the intricate effects that local chromatin organization can have on gene expression.

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Posted February 26, 2014.
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Chromatin loops as modulators of enhancer-promoter interactions in their vicinity
Boryana Doyle, Geoffrey Fudenberg, Maxim Imakaev, Leonid A. Mirny
bioRxiv 003087; doi: https://doi.org/10.1101/003087
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Chromatin loops as modulators of enhancer-promoter interactions in their vicinity
Boryana Doyle, Geoffrey Fudenberg, Maxim Imakaev, Leonid A. Mirny
bioRxiv 003087; doi: https://doi.org/10.1101/003087

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