‘Stretch enhancers’ influence cell-specific gene expression variants associated with type 2 diabetes, other diseases

Farmington, Conn.—A research team led by National Institutes of Health Director Francis Collins, M.D,, Ph.D., and including Jackson Laboratory Assistant Professor Michael Stitzel, Ph.D., has published a report on the important role of "stretch enhancers"—long genomic sequences that act as a kind of rheostat to amp up gene expression levels—in coordinating cell type-specific regulatory programs.

The report, in the Proceedings of the National Academy of Sciences, also notes that genetic variants linked to type 2 diabetes and other diseases are also common in stretch enhancers. "Notably," the researchers state in the report, "stretch enhancers specific to pancreatic islets harbor variants linked to type 2 diabetes and related traits."

Stitzel, who studies the genetics, genomics and epigenomics of islet dysfunction and type 2 diabetes, explains, "Stretch enhancer locations are unique to each cell type. They guide cell type-specific gene expression patterns, and are enriched for SNPs (single-nucleotide polymorphisms) in genome-wide association studies. Together, this suggests that understanding and manipulating their activity may provide a new avenue for cellular reprogramming and therapeutic development."

Stitzel joined The Jackson Laboratory faculty in Connecticut in September, following a postdoctoral appointment in Collins' laboratory at the National Human Genome Research Institute (NHGRI).

Several recent studies have shown that non-coding regulatory elements in the genome are linked to common diseases, coauthor Stephen Parker, Ph.D., of NHGRI, says, "but our finding that stronger signals come from these big, stretch enhancer regions helps illuminate the really important parts of the genome. Looking forward, it's clear these regions will be critical to understanding disease diagnosis, prognosis and treatment."

The Jackson Laboratory is an independent, nonprofit biomedical research institution based in Bar Harbor, Maine, with a facility in Sacramento, Calif., and a new genomic medicine institute in Farmington, Conn. It employs a total staff of more than 1,500. Its mission is to discover precise genomic solutions for disease and empower the global biomedical community in the shared quest to improve human health.

Parker, Stitzel et al.: Chromatin stretch enhancer states drive cell specific gene regulation and harbor human disease risk variants. Proceedings of the National Academy of Sciences.