Chromosomes have yet another level of complexity and are even better designed than previously thought. Erez Lieberman-Aiden et al
By probing the three-dimensional architecture of whole genomes, the authors constructed spatial proximity maps of the human genome that confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. They identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus.
Imagine a fine hair 2 meters long. Imagine balling it up in such a way that it can fit on the head of pin — and be unraveled and knot-free, at a moment’s notice. A similar engineering feat is at work inside each cell in our body. The genome is over two meters long and must be carefully packed into the confines of a space (called the “nucleus”) several times narrower than a human hair.
First co-author Erez Lieberman-Aiden, says “Scientists have not really understood how the double helix folds to fit into the nucleus of a human cell, which is only about a hundredth of a millimeter in diameter.”
They discovered an unusual compartmental structure to DNA within the nucleus: active genes tend to localize to one area and inactive ones to another. Also the genomic regions appear to flow in and out of these two nuclear compartments as the genes within them are turned on or off.
“Cells cleverly separate the most active genes into their own special neighborhood, to make it easier for proteins and other regulators to reach them,” said Dekker, an associate professor of biochemistry and molecular pharmacology. The finer-scale organization of the genome inside nucleus is achieved by folding into what is known as a “fractal globule,” DNA condenses into an exceedingly dense structure, entirely devoid of knots, that can easily unfold and refold as needed.
“Nature’s devised a stunningly elegant solution to storing information – a super-dense, knot-free structure,” said senior author Eric Lander, who is also professor of biology at MIT, and professor of systems biology at Harvard Medical School. It is well known that DNA elements separated by vast genomic distances can – and do – interact with each other, but it has only recently become possible to map these interactions on a genome-wide scale.
Adapted from a press release written by Steve Bradt, Harvard University