As part of an unprecedented study, scientists from the MRC Laboratory of Molecular Biology and the University of Cambridge has developed the first ever complete model of mammalian genomes present in every individual cell of an organism. Showcased in the form of 3D images, these structures provide an accurate representation of how the long chains of DNA fit inside the cellular nuclei.
With the help of advanced imaging technologies, the team was able to identify nearly 100,000 different points of one of the DNA strands that make up the genome in a murine embryonic stem cell. As explained by the researchers, stem cells are the most fundament cells (or “master cells”) that in turn differentiate to form most other types of cells.
If you recall your eighth -grade science, chromosomes are usually associated with the shape ‘X’. According to the team, however, they take this shape only after the cell undergoes division. The new study marks the first time that scientists have managed to accurately discern the structures and arrangements of active chromosome, and also the way they come together to form complete genomes.
The knowledge of how DNA strands fold inside a nucleus, the researchers believe, would in turn enhance our understanding of how individual genes and DNA segments interact with one another. The significance of the breakthrough lies in the fact that the genome’s structure and arrangement play a major role in switching specific genes “on” and “off”, especially during disease.
In the featured image, each of the 20 chromosomes in a mouse embryonic stem cell is represented in a particular color. The following video shows the different regions of active genes (in blue) and inactive ones (yellow) inside the chromosomes. As depicted in the clip, the active genetic sections usually occur along the genome’s interior, and are separated from more dormant ones that interact with the dense fibril-lined nuclear network called the nuclear lamina.
According to Ernest Laue, a professor at the University of Cambridge’s Department of Biochemistry and a member of the research team, the same arrangement of genome in each cell in turn suggests that chromosomal folding probably plays a part in regulating a variety of important processes like DNA replication as well as cell division. Speaking about the findings, recently published in the Nature journal, he said:
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. In the future, we’ll be able to study how these 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.
For the study, jointly funded by the European Union, the Wellcome Trust and the Medical Research Council, scientists from Cambridge’s Departments of Chemistry, Biochemistry and the Wellcome-MRC Stem Cell Institute collaborated with MRC Laboratory of Molecular Biology. Dr. Tom Collins of the Wellcome team added:
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.
Source: University of Cambridge