Researchers have revealed the three dimensional arrangement of intact genomes in individual mammalian cells, illustrating that the DNA of all chromosomes folds in a specific way inside of the nucleus of cells. Scientists at the University of Cambridge and the MRC Laboratory of Molecular Biology utilized powerful imaging techniques and took around 100,000 measurements for this analysis of the genome in a mouse embryonic stem cell.
Chromosomes only take on their typically known, X shape when the cell is dividing. Knowing how the genome is arranged during other critical times will give scientists insight into gene regulation and interaction, and could provide insight into processes like development. Understanding how these processes work under normal conditions can also help understand dysfunction and abnormalities. The researchers have created videos to animate their findings, which are reported in Nature.
The structure has been animated in accompanying videos, which illustrate the whole genome from a mouse embryonic stem cell. In the video above, the 20 different chromosomes of the cell have been colored differently. The second video, below, highlights regions of the chromosomes where there is gene activity by coloring them in blue, while areas that associate with a part of the nucleus, the nuclear lamina, are highlighted in yellow. It's thus possible to see an arrangement placing the most active areas go the genome towards the interior, and are separate from less active areas, which interact with the nuclear lamina. It was observed that this arrangement is consistent from cell to cell, suggesting that this organization could be important to other cellular processes like the three dimensional arrangement of the genome. It would then also likely be playing a role in DNA replication and cell division.
"Knowing where all the genes and control elements are at a given moment will help us understand the molecular mechanisms that control and maintain their expression," said Professor Ernest Laue, whose research team at Cambridge's Department of Biochemistry worked to develop this method.
"Visualizing a genome in 3D at such an unprecedented level of detail is an exciting step forward in research and one that has been many years in the making. This detail will reveal some of the underlying principles that govern the organization of our genomes - for example how chromosomes interact or how structure can influence whether genes are switched on or off. If we can apply this method to cells with abnormal genomes, such as cancer cells, we may be able to better understand what exactly goes wrong to cause disease, and how we could develop solutions to correct this," commented Dr Tom Collins of Wellcome's Genetics and Molecular Sciences team.
"In the future, we'll be able to study how this changes as stem cells differentiate and how decisions are made in individual developing stem cells. Until now, we've only been able to look at groups, or 'populations', of these cells and so have been unable to see individual differences, at least from the outside. Currently, these mechanisms are poorly understood and understanding them may be key to realizing the potential of stem cells in medicine," concluded Laue.