The long-range interaction landscape of gene promoters
Sanyal A, Lajoie BR, Jain G, Dekker J. The long-range interaction landscape of gene promoters. Nature. 2012 Sep 6;489(7414):109-13. doi: 10.1038/nature11279. PMID: 22955621; PMCID: PMC3555147.
Using 5C maps of cell lines this study investigated long range interactions between promoters and distal sites including enhancers, other promoters, and CTCF-bound sites. The locations studies were part of 44 ENCODE pilot project regions spanning 1% of the genome containing regions between 500 kb and 1.9 Mb with 628 TSS and 4,535 distal elements in the fragments. Within a regions, loci close to each other interact more than loci further apart. Similarly, loci on the same chromosome interact more often than loci on different chromosomes because of the formation of chromosome territories.
They found correlations between gene expression, promoter-enhancer interactions and enhancer RNA (eRNA). The long-range interactions tended to be with elements ~120kb upstream of the TSS and were not blocked by CTCF-bound sites. These genomic elements and their multiple interactions form networks. They show that the nearest gene is not a good predictor of long-range interactions as only 7% of the looping interactions were with the nearest gene. Looping interactions were composed of enchancer, weak enchancers, CTCF elements, and actively transcribed chromatin but did not have as much repressed chromatin. Looking at eRNAs, they found that enchancers looping to TSSs are more likely to express eRNAs than non-looping enhancers. Expressed TSSs have more interactions with enhancers, promoters and CTCF than non-expressed TSSs. CTCF interactions seemed to block 58% of interactions at sites with CTCF and cohesin.