Now that the Olympic games are over, researchers in the ENCODE consortium have announced that they’ve just finished another Olympic effort of their own—the large-scale mapping of functional elements in the human genome. And just like the flexible “Fierce Five” U.S. women’s gymnastics team, it turns out that the genome is very bendy, looping around so that promoters can interact with elements that are far away, say researchers.
The team, which is at the U. Mass Medical School, used chromosome conformation capture carbon copy (5C) to comprehensively study these long-range interactions between promoters and “distal” elements. With 5C, they can target two sets of genomic loci at single restriction-fragment resolution in high-throughput to see whether the sites associate. They used this method on promoters and distal elements in three cell lines and integrated these data with those that the ENCODE teams generated.
The data gave them a way to think about regulatory elements and genes in 3-D space. In a nutshell, it’s loopy. They found more than 1000 of these long-range interactions, in all three cell lines, between promoters and far-away sites like enhancers, other promoters, and sites that had CTCF bound to them (CTCF helps DNA form loops). Some of the interactions were cell type-specific, and many had active-chromatin histone mods. The interactions were asymmetric, most of them happening about 120 kb upstream of a TSS. One surprise was that elements, like enhancers, don’t necessarily interact with the closest TSS.
Do some mental gymnastics and read the paper at Nature, September 2012.