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What does a chromosome really look like?

An image of a chromosome generated by Peter’s 3D modeling technique. (Image credit: Drs Tim Stevens and Takashi Nagano, Babraham Institute)

An image of a chromosome generated by Peter’s 3D modeling technique. (Image credit: Drs Tim Stevens and Takashi Nagano, Babraham Institute)

You’d be forgiven for thinking that all chromosomes are X-shaped bundles. But new research MRC-funded research has shown that they spend most of their time looking more like a tangled mass of string, as Peter Fraser, a researcher at the Babraham Institute, explains. 

The image of a chromosome as an X-shaped blob is familiar to many. But perhaps not everyone knows that this microscopic portrait of a chromosome shows a structure that occurs only transiently in cells, at a point when they are just about to divide by undergoing a process called mitosis.

The vast majority of cells in an organism have finished dividing and their chromosomes don’t look anything like the familiar X-shape. Even cells that are still in the business of dividing, such as blood and skin cells, spend most of their time in a kind of ‘resting’ non-mitotic state. But what do chromosomes in these cells look like?

So far it has been impossible to create accurate pictures of these chromosomes — existing techniques can only determine the average structure of chromosomes from millions of cells. But it’s important that we know what they look like because, far from resting, it’s in this non-mitotic state that all of the important functions of the genome are operating and controlled.

Furthermore, the latest research shows that the structure of these chromosomes, and the way the DNA within them folds up, is intimately linked to when and how much genes are used, which has consequences for normal health, ageing and disease.

We have developed a new method, which we describe in a paper in the journal Nature today, that involves creating thousands of molecular measurements of chromosomes in single cells using high-throughput DNA sequencing. By combining these measurements using powerful computers we can for the first time create a three-dimensional model of resting chromosomes.

This gives us not only the structure of the chromosome, but also means we can map the specific DNA sequence onto it, allowing us to see where specific genes and other important genomic features are on a 3D structure. For example, we found that active regions — containing genes that are used frequently — tend to be located on the outside of chromosomes for easy access by the cell machinery responsible for gene expression.

Using these 3D models, we have begun to unravel the basic principles of chromosome structure and its role in how our genome functions.

Peter Fraser

Read a BBSRC article about this research, which includes a video describing the structure of chromosomes.

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