Identification of multi-loci hubs from 4C-seq demonstrates the functional importance of simultaneous interactions

Use of low resolution single cell DNA FISH and population based high resolution chromosome conformation capture techniques have highlighted the importance of pairwise chromatin interactions in gene regulation. However, it is unlikely that associations involving regulatory elements act in isolation o...

Full description

Saved in:
Bibliographic Details
Published in:Nucleic acids research 2016-10, Vol.44 (18), p.8714-8725
Main Authors: Jiang, Tingting, Raviram, Ramya, Snetkova, Valentina, Rocha, Pedro P, Proudhon, Charlotte, Badri, Sana, Bonneau, Richard, Skok, Jane A, Kluger, Yuval
Format: Article
Language:English
Subjects:
Chromatin - metabolism
Chromosomes - metabolism
Enhancer Elements, Genetic
Estrogen Receptor beta - metabolism
Gene regulation, Chromatin and Epigenetics
Genetic Loci
Genome
Nucleic Acid Conformation
Receptors, Antigen, T-Cell, alpha-beta
Sequence Analysis, DNA - methods
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Use of low resolution single cell DNA FISH and population based high resolution chromosome conformation capture techniques have highlighted the importance of pairwise chromatin interactions in gene regulation. However, it is unlikely that associations involving regulatory elements act in isolation of other interacting partners that also influence their impact. Indeed, the influence of multi-loci interactions remains something of an enigma as beyond low-resolution DNA FISH we do not have the appropriate tools to analyze these. Here we present a method that uses standard 4C-seq data to identify multi-loci interactions from the same cell. We demonstrate the feasibility of our method using 4C-seq data sets that identify known pairwise and novel tri-loci interactions involving the Tcrb and Igk antigen receptor enhancers. We further show that the three Igk enhancers, MiEκ, 3'Eκ and Edκ, interact simultaneously in this super-enhancer cluster, which add to our previous findings showing that loss of one element decreases interactions between all three elements as well as reducing their transcriptional output. These findings underscore the functional importance of simultaneous interactions and provide new insight into the relationship between enhancer elements. Our method opens the door for studying multi-loci interactions and their impact on gene regulation in other biological settings.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkw568