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BOSTON – The three-dimensional structure of the human genome has been deciphered by scientists.
The breakthrough will pave the way for new insights into genomic function and expanding our understanding of how cellular DNA folds at scales that dwarf the double helix.
In a paper featured this week on the cover of the journal Science, they describe a new technology called Hi-C and apply it to answer the thorny question of how each of our cells stows some three billion base pairs of DNA while maintaining access to functionally crucial segments.
The paper comes from a team led by scientists at Harvard University, the Broad Institute of Harvard and MIT, University of Massachusetts Medical School, and the Massachusetts Institute of Technology.
“We’ve long known that on a small scale, DNA is a double helix,” says co-first author
“But if the double helix didn’t fold further, the genome in each cell would be two meters long. 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,” the expert added.
The researchers report two striking findings. First, the human genome is organized into two separate compartments, keeping active genes separate and accessible while sequestering unused DNA in a denser storage compartment. Chromosomes snake in and out of the two compartments repeatedly as their DNA alternates between active, gene-rich and inactive, gene-poor stretches.
“Cells cleverly separate the most active genes into their own special neighborhood, to make it easier for proteins and other regulators to reach them,” says Job Dekker, associate professor of biochemistry and molecular pharmacology at UMass Medical School and a senior author of the Science paper.
Second, at a finer scale, the genome adopts an unusual organization known in mathematics as a “fractal.” The specific architecture the scientists found, called a “fractal globule,” enables the cell to pack DNA incredibly tightly — the information density in the nucleus is trillions of times higher than on a computer chip-while avoiding the knots and tangles that might interfere with the cell’s ability to read its own genome. Moreover, the DNA can easily unfold and refold during gene activation, gene repression, and cell replication.