“To determine genome structure without being able to directly see it, the researchers first soaked cell nuclei in formaldehyde, which interacts with DNA like glue. The formaldehyde stuck together genes that are distant from each other in linear genomic sequences, but adjacent to each other in actual three-dimensional genomic space.
The researchers then added a chemical that dissolved the gene-by-gene linear sequence bonds, but left the formaldehyde links intact. The result was a pool of paired genes, something like a frozen ball of noodles that had been sliced into a million fragmentary layers and mixed.
By studying the pairs, the researchers could tell which genes had been near each other in the original genome. With the aid of software that cross-referenced the gene pairs with their known sequences on the genome, they assembled a digital sculpture of the genome. And what a marvelous sculpture it is.
“There’s no knots. It’s totally unentangled. It’s like an incredibly dense noodle ball, but you can pull out some of the noodles and put them back in, without disturbing the structure at all,” said Harvard University computational biologist Erez Lieberman-Aiden, also a study co-author.
In mathematical terms, the pieces of the genome are folded into something similar to a Hilbert curve, one of a family of shapes that can fill a two-dimensional space without ever overlapping — and then do the same trick in three dimensions.”
To say this is an astounding breakthrough is an understatement.