Tuesday, 18 April 2017

Visualizing the genome: First 3-D structures of active DNA created


Researchers from the University of Cambridge and the MRC Laboratory of Molecular Biology used a combination of imaging and up to 100,000 measurements of where different parts of the DNA are close to each other to examine the genome in a mouse embryonic stem cell. Stem cells are 'master cells', which can develop -- or 'differentiate' -- into almost any type of cell within the body.

Most people are familiar with the well-known 'X' shape of chromosomes, but in fact chromosomes only take on this shape when the cell divides. Using their new approach, the researchers have now been able to determine the structures of active chromosomes inside the cell, and how they interact with each other to form an intact genome. This is important because knowledge of the way DNA folds inside the cell allows scientists to study how specific genes, and the DNA regions that control them, interact with each other. The genome's structure controls when and how strongly genes -- particular regions of the DNA -- are switched 'on' or 'off'. This plays a critical role in the development of organisms and also, when it goes awry, in disease.

The researchers have illustrated the structure in accompanying videos, which show the intact genome from one particular mouse embryonic stem cell. In the film, above, each of the cell's 20 chromosomes is coloured differently.


In a second video regions of the chromosomes where genes are active are coloured blue, and the regions that interact with the nuclear lamina (a dense fibrillar network inside the nucleus) are coloured yellow. The structure shows that the genome is arranged such that the most active genetic regions are on the interior and separated in space from the less active regions that associate with the nuclear lamina. The consistent segregation of these regions, in the same way in every cell, suggests that these processes could drive chromosome and genome folding and thus regulate important cellular events such as DNA replication and cell division.

For further details see:

Stevens, TJ et al. 3D structures of individual mammalian genomes studied by single-cell Hi-C. Nature, 3 March 2017 DOI: 10.1038/nature21429

Posted by Dr. Tim Sandle

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