Using a new method developed in the Lieb laboratory called FAIRE-seq, Lieb and his colleagues isolated and sequenced a total of 80,000 open chromatin sites within pancreatic islet cells. They then compared these sites to those in non-islet cells to narrow the number down to 3,300 clusters of sites specific to this cell type. Each cluster typically encompassed single genes that are active specifically in islet cells. Twenty of these genes are known to harbor gene variants associated with type II diabetes.

The researchers decided to continue their studies on the variant most strongly associated with the disease, a single nucleotide polymorphism - or SNP - occurring in the TCF7L2 gene. They found that the chromatin is more open in the presence of the high risk version of the gene (a T) than in the presence of the non-risk version (an A). Further analysis demonstrated that the risk variant enhanced the activity of the gene, indicating that it may possess functional characteristics that could contribute to disease.

Lieb says his map is likely to help others within the diabetes research community identify new targets for understanding - and ultimately treating - the disease more effectively. But the approach is not limited to diabetes, or even pancreatic islet cells. He plans to use FAIRE-seq to chart the open chromatin regions present within other cells, such as the immune system's lymphocytes.

Source: University of North Carolina School of Medicine