Once thought to be monogamous molecules characterized by devote linear relationships, chromosomes turn out to be philandering conformation-changers with burning loins of desire concealed between their genes. Coming from the lab of Bing Ren at the University of California, San Diego, a massive analysis of genome-wide chromosome interactions captured by Hi-C uncovers a distinct piece of nuclear architecture: Frequently Interacting REgions (FIREs).
The talented team examined 14 primary tissues from 4 healthy human donors along with 7 common cultured cell lines. This tricky task was achieved by making use of some previously published data sets as well as developing a novel Poisson-regression-based normalization approach that they termed as ‘‘HiCNormCis’’.
Here’s what they found:
- FIREs are promiscuous genomic regions that prefer more than the standard twosome of typical chromatin contacts and can even get intimate with each other.
- Rather than occurring at the anchor points of chromatin loops, FIREs live in the middle of loops and are free to explore their neighborhoods.
- Despite their promiscuous nature, FIREs are quite selective when it comes to tissue specificity, as almost 60% are found in only one or two of the tissues and cell lines investigated.
- FIREs are active regulatory regions that are enriched for active chromatin marks (H3K27ac and H3K4me1), are found at active enhancers, particularly super-enhancers, and reside near active cell-identity genes.
- Even more active are clusters of FIREs, known as super-FIREs.
- While they have many local (<200 kb) interactions, FIREs give new meaning to a long-distance relationship, since they often reach ~500-kb and can even go up to 2 Mb.
- FIREs are conserved in human and mouse tissues and depend on the tinder of the CTCF/Cohesin complex.
In addition to being a new piece of nuclear architecture that will make sure you’ll never look at chromatin the same way again, FIREs can also be used to understand all those non-coding GWAS hits. Through data mining, it became apparent that tissue specific FIREs are enriched at disease-associated SNPs in the relevant tissue.
Go ignite your passion for chromatin over at Cell Reports, November 2016
And if you want to read around with other journals, go have a look at the rest of the 41 new papers from the International Human Epigenome Consortium (IHEC) and their open data portal.