Learning the Alphabet of Controlling Gene Expression
News Jan 21, 2013
In a new study, published in the journal Cell, they identified the DNA sequences that bind to over four hundred proteins that control expression of genes. This knowledge is required to understand how differences in genomes of individuals affect their risk to develop disease.
After the human genome was sequenced in 2000, it was hoped that the knowledge of the entire sequence of human DNA could rapidly be translated to medical benefits such as novel drugs, and predictive tools that would identify individuals at risk of disease. This, however, turned out to be harder than anticipated, one of the reasons being that only 1 percent of the genome that code for proteins was in fact possible to read. The remaining part, much of which describes how these proteins should be expressed in different cells and tissues, could not be understood. This, in turn, because the scientists did not know which DNA sequences are functional, and bind to the specific proteins called transcription factors that regulate gene expression.
"The genome is like a book written in a foreign language, we know the letters but cannot understand why a human genome makes a human or the mouse genome a mouse", says Professor Jussi Taipale, who led the study at the Department of Biosciences and Nutrition. "Why some individuals have higher risk to develop common diseases such as heart disease or cancer has been even less understood."
The human genome encodes approximately 1000 transcription factors, and they bind specifically to short sequences of DNA, and control the production of other proteins. In the work published in Cell, the scientists at Karolinska Institutet describe DNA sequences that bind to over 400 such proteins, representing approximately half of all human transcription factors. Data was generated with a new method that uses a modern DNA sequencer that produces hundreds of millions of sequences, giving the results unprecedented accuracy and reliability.
In addition, binding specificities of human transcription factors were compared to those of the mouse. Surprisingly, no differences were found. According to the scientists, these results suggest that the basic machinery of gene expression is similar in humans and mice, and that the differences in size and shape are caused not by differences in transcription factor proteins, but by presence or absence of the specific sequences that bind to them.
"Taken together, the work represents a large step towards deciphering the code that controls gene expression, and provides an invaluable resource to scientists all over the world to further understand the function of the whole human genome", says Professor Taipale. The resulting increase in our ability to read the genome will also improve our ability to translate the rapidly accumulating genomic information to medical benefits.
Previous work by the International Multiple Sclerosis Genetics Consortium (IMSGC) has identified 233 genetic risk variants. However, these only account for about 20% of overall disease risk, with the remaining genetic culprits proving elusive. A new study has tracked down four of these hard-to-find genes.READ MORE
Scientists at McGill have found the answer to a question that perplexed Charles Darwin; if natural selection works at the level of the individual, fighting for survival and reproduction, how can a single colony produce worker ants that are so dramatically different in size – from “minor” workers to large-headed soldiers with huge mandibles – especially if they are sterile?
5th International Congress on Epigenetics & Chromatin
Aug 22 - Aug 23, 2019
International Conference on e-Health and Healthcare Innovations
May 08 - May 09, 2019
4th Annual Congress on Nanomedicine and Drug Delivery
Apr 04 - Apr 06, 2019