Capturing the genome

Your body is a community of approximately 37 trillion1 cells – tiny structures of all shapes and sizes that work together to allow you to move, eat, breathe, sleep and perform all manner of other unpleasant bodily functions. Each cell has its own, specific, specialized job – but how does it know what to do, and when? How does a cell in the eye detect light, or a blood cell detect an infection?

The answers are found in the DNA molecule that sits at the center of each cell. DNA contains all the information required to build an entire human being and as a result, it’s pretty big. Each 0.1mm cell packs in about 2 metres of DNA – a storage solution that even IKEA would be proud of. How this spectacular feat is achieved and each cell still manages to access the specific information it requires to do its job is a hot topic in biological research, and one which is addressed in a recent paper published by scientists at the WIMM.

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Image copyright: Ross Thorne (2014)

Scientists have long thought that the physical packaging of DNA required to fit it inside the cell may bring specific parts of these immensely long molecules into contact with each other2, although what these regions are and why this might happen was unknown. New technologies to sequence DNA with high speed and precision have been emerging at an almost exponential rate in recent years3 and these advances have allowed scientists to show that specific regions of DNA interact.  What’s more, these exchanges seem to involve particular regions of the DNA that control a cells function.

Until now scientists have had to make the choice between looking at large bits of the DNA at low resolution, like a very badly pixelated picture of a landscape, or to zoom in and get a single sharp image of a small part of the picture4.  However, thanks to a new technique developed by a team led by Dr. Jim Hughes at the WIMM, that could all be about to change. The method, called Capture-C5, allows researchers to take hundreds (and potentially thousands) of high-resolution pictures of the interactions within regions of the DNA of interest, so a much sharper overall picture of the interaction landscape can be built up.

This methodological breakthrough holds huge promise for analyzing the 3D structure of the genome and how it affects cell function. Scientists have long wondered whether variations in these interacting DNA sequences might affect our chances of getting a particular disease, but due to the limitations of available technologies they have been unable to test this – until now.  Watch this space…

Post written by Bryony Graham.

 

References

  1. http://www.ncbi.nlm.nih.gov/pubmed/23829164
  2. Cremer, T. and Cremer, C. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nature Reviews Genetics 2, pg. 292-301 (2001)
  3. Mardis, E. R. Next-Generation Sequencing Platforms. Annual Review of Analytical Chemistry. 6, pg. 287-303 (2013)
  4. De Wit, E. and de Laat, W. A decade of 3C technologies: insights into nuclear organization. Genes & Development 26, pg. 11-24 (2012)
  5. Hughes, J. R., Roberts, N., McGowan, S., Hay, D., Giannoulatou, E., Lynch, M., De Gobbi, M., Taylor, S., Gibbons, R., Higgs, D. R. Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment. Nature Genetics 46, pg. 205-212 (2014)