Wednesday, July 4, 2012

Mouse 'junk' DNA vital for gene regulation

Some junk is worth keeping. Non-coding, or junk, mouse DNA contains vast amounts of information vital to gene function ? and those regulatory functions take up much more space on the genome than the all-important coding segments.

Less than 2 per cent of DNA actually codes for proteins, so the double helix is responsible for a great deal more than making proteins. Some segments are designated enhancers and promoters. These bind transcription factors that allow coding DNA to be read and translated into proteins. Other regions, called insulators, prevent neighbouring genes from being read together accidentally.

To work out which sections of DNA might contain these segments ? collectively known as cis-regulatory elements ? Bing Ren at the Ludwig Institute for Cancer Research at the University of California, San Diego and colleagues looked at the genomes of 19 types of mouse tissue.

Protein-coding genes can be identified by tracing back through proteins and RNA. But to identify the regulatory elements, researchers had to look at the structure of DNA itself. They used subtle differences in histones, the proteins around which DNA is wound, to predict whether a segment of DNA served as a promoter, enhancer or insulator. The method yielded more than 300,000 functional elements from the genomes of the tissues they examined.

Taken together, the 300,000 regulatory regions comprised 11 per cent of the mouse genome. "What the study tells us is that cis-regulatory regions cover more than five times as much space as protein-coding regions," says Feng Yue, also at the Ludwig Institute and a member of the research team.

The data could be useful for understanding human genetics as well. Using data from comparative genetic studies, the researchers found that the 300,000 functional elements make up about 70 per cent of the evolutionarily conserved non-coding DNA shared by mice and humans.

Even though the human genome was sequenced over a decade ago, gaps like these demonstrate just how little we know about what the large portions of those DNA sequences actually do.

Journal reference: Nature, DOI: 10.1038/nature11243

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