October 9, 2009

Researchers Decode 3D Structures Of The Human Genome

Scientists have finally cracked the code of the three dimensional structure of the human genome. This could lead to a better understanding of the function and structures of cellular DNA and how it folds at scales that dwarf the double helix, according to a report published Thursday.

"By breaking the genome into millions of pieces, we created a spatial map showing how close different parts are to one another," said Nynke van Berkum, one of two primary authors of the study, which appears in the journal Science.

"We made a fantastic three-dimensional jigsaw puzzle and then, with a computer, solved the puzzle," said Berkum, a postdoctoral researcher at University of Massachusetts Medical School.

Scientists accomplished this by using a new technology called 'Hi-C' that enables them to solve the mystery of how every single human cell could contain some three million pairs of base DNA while still accessing functionally crucial segments.

"We've long known that on a small scale, DNA is a double helix. But if the double helix didn't fold further, the genome in each cell would be two meters long," said Erez Lieberman-Aiden, a graduate student in the Harvard-MIT Division of Health Science and Technology and a researcher at Harvard and the Broad Institute.

"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. This new approach enabled us to probe exactly that question," said Lieberman-Aiden, the study's other main author.

What the researchers discovered is that the human genome is arranged in two distinct compartments that let active genes remain accessible to proteins while being kept apart from the densely packed stores of inactive DNA.

Chromosomes travel back and forth between compartments as their DNA switches from active to inactive stretches of the genome.

The finding showed how the genome uses an odd method of organization known in mathematics as a "fractal" that allows the cell to stuff DNA into its nucleus at a density three trillion times greater than a computer chip.

That is all done while simultaneously bypassing knots and tangles that might hinder the cell's ability to read its own genome, while enabling the DNA to unfold and refold easily during gene activation, gene repression, and cell replication.

"Nature's devised a stunningly elegant solution to storing information, a super-dense, knot-free structure," says senior author Eric Lander, director of the Broad Institute.


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