A model to decipher the complexity of gene regulation

phys.org | 8/20/2015 | Staff
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How, where and when genes are expressed determine individual phenotypes. If gene expression is controlled by many regulatory elements, what, ultimately, controls them? And how does genetic variation affect them? The SysGenetiX project, led by the University of Geneva (UNIGE) in collaboration with the University of Lausanne (UNIL), Switzerland, sought to investigate these regulatory elements, as well as the manifold interactions between them and with genes, with the ultimate goal of understanding the mechanisms that render some people more predisposed to manifesting particular diseases than others.

By studying chromatin modifications (i.e. how the genome is "packaged") in the cells of about 300 individuals, scientists from Geneva and Lausanne not only identified the structure of these regulatory elements, they were also able to model how their interactions throughout the whole genome influence gene regulation and risk of disease. Their approach is now published in Science.

Emmanouil - Dermitzakis - Leader - SysGenetiX - Project

Emmanouil Dermitzakis, leader of the SysGenetiX project, is a specialist of the genetic variation of gene regulation. He explains the novel approach of this work: "Instead of only studying the levels of gene expression—a strategy that gives only a partial picture—we decided to focus on chromatin, which seems to be an intermediate molecular component of regulation."

Chromatin, a complex of DNA, RNA and proteins, plays important roles in protecting DNA during crucial phases of the cell cycle. Chromatin modifications therefore mediate the effects of expression factors, and eventually regulate gene expression. By measuring the activity of regulatory elements in chromatin profiles, the scientists were able to capture the levels of activity of most regulatory elements.

Approach - Settings - Studies - Olivier - Delaneau

"We had tested our approach on more focused settings in past studies," says Olivier Delaneau, a researcher in Prof. Dermitzakis' lab and first author of this work. "This time, we wanted to study chromatin profiles of large samples to be able to understand, at population...
(Excerpt) Read more at: phys.org
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