Three-Dimensional Genome
New technology reveals the higher-order structure of DNA
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No knots DNA may be packed inside cell nuclei as a compact, unknotted structure called a fractal globule.
Credit: Leonid A. Mirny and Maxim Ima Kaev/Science
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Results: Scientists developed a tool that makes it possible to map the three-dimensional structure of the entire human genome, shedding light on how six feet of DNA is packed into a cell nucleus about three micrometers in diameter. According to the resulting analysis, chromosomes are folded so that the active genes—the ones this particular cell is using to make proteins—are close together.
Why it matters: Growing evidence suggests that the way the genome is packed in a particular cell is key to determining which of its genes are active. The new findings could allow scientists to study this crucial aspect of gene regulation more precisely.
Methods: Scientists treated a folded DNA molecule with a preservative in order to create bonds between genes that are close together in the three-dimensional structure even though they may be far apart in the linear sequence. Then they broke the molecule into a million pieces using a DNA-cutting enzyme. The researchers sequenced these pieces to identify which genes had bonded and then used this information to develop a model of how the chromosome had been folded.
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Next steps: Scientists plan to study how the three-dimensional structure of the genome varies between different cell types, between different organisms, and between normal and cancerous cells. They also hope that improving the resolution of the technology might reveal new structural properties of the genome.
Source: “Comprehensive Mapping of Long-range Interactions Reveals Folding Principles of the Human Genome” by Eric S. Lander, Job Dekker, et al.; Science 326: 289–293.
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