Monday, October 19, 2009

Investigators Reveal Folding Principles of the Human Genome

Scientists have long been speculating on how DNA gets packaged inside chromosomes while remaining readable and easily accessible. In a paper just published in Science, researchers from Harvard and MIT have discovered that sections of the DNA bunch together into 'fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus.' The image on the side shows the 'equilibrium globule' configuration that was thought to be the structure (left) and the actual configuration (right) that was identified by the team.
Key to deciphering the genome's structure was the development of the new Hi-C technique, which permits genome-wide analysis of the proximity of individual genes. The scientists first used formaldehyde to link together DNA strands that are nearby in the cell's nucleus. They then determined the identity of the neighboring segments by shredding the DNA into many tiny pieces, attaching the linked DNA into small loops, and performing massively parallel DNA sequencing.
Lieberman-Aiden observed that the data suggest a fractal globule. He then teamed up with Mirny and Mirny's student Maxim Imakaev to confirm his hypothesis and demonstrate conclusively that the Hi-C data matched fractal globule behavior. Computer simulations further helped to reveal biologically important features of such a DNA architecture.
In future experiments, the researchers hope to follow the development of stem cells into mature cell types such as kidney cells, says Lieberman-Aiden. 'We want to understand how that process takes place, because it clearly involves some 3-D remodeling of the nucleus.'
Press release: A new dimension for genome studies...

Abstract in Science: Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome


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