Scientists Discover 3D Genome Structure

A team of scientists at Harvard, MIT, the Broad Institute of Harvard and MIT, and the University of Massachusetts Medical School announced yesterday that they have deciphered the three-dimensional structure of the human genome.

This discovery expands the current understanding of how cellular DNA folds at scales more miniscule than the double helix.

“Scientists have not really understood how the double helix folds to fit into the nucleus of a human cell,” said co-first author Erez Lieberman-Aiden, a researcher at Harvard’s School of Engineering and Applied Sciences and in the laboratory of Eric S. Lander at the Broad Institute. “This new approach enabled us to probe exactly that question.”

In the paper featured this week on the cover of the journal entitled “Science”, the researchers reported two major findings that contributed to answering how our cells stowed three billion base pairs of DNA while maintaining access to functionally crucial segments.

First, the scientists discovered that human genome is divided into two separate compartments of active genomes and unused DNA.

Chromosomes repeatedly snake in and out of the two compartments 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,” said Job Dekker, a senior author of the paper and associate professor at UMass Medical School.

Second, scientists observed that DNA was compressed into an architecture called a “fractal globule”.

This configuration deviates from the previously-proposed configuration of an “equilibrium globule”, and allows cells to pack DNA incredibly tightly while avoiding knots and tangles that might interfere with the cell’s ability to read its own genome.

“Nature’s devised a stunningly elegant solution to storing information—a super-dense, knot-free structure,” said senior author Eric S. Lander, director of the Broad Institute.

Key to the current work has been the development of a new Hi-C technology, which allowed researchers to create a spatial map to conduct genome-wide analysis of the proximity of individual genes.

“This paper offers just a rough sketch of the genome, and the technology is capable of offering a much higher resolution picture,” Lieberman-Aiden said.

“We’d like to try and do more sequencing so that we can understand things in a higher resolution,” he said.

—Staff writer Manning Ding can be reached at ding3@fas.harvard.edu