Clusters of islet enhancers may contribute to risk for type 2 diabetes
Sequence variations in islet enhancer clusters may contribute to the risk for type 2 diabetes and variations in fasting glucose levels, according to data published in Nature Genetics. These data may better explain the transcriptional program of pancreatic beta cells and the underlying molecular mechanisms of type 2 diabetes, researchers wrote.
“Non-coding DNA, or junk DNA as it is sometimes known, is the dark matter of the genome. We’re only just beginning to unravel what it does,” Jorge Ferrer, MD, PhD, a Wellcome Trust senior investigator from the department of medicine at Imperial College London, said in a press release.
Ferrer and colleagues mapped and examined the function of human islet cis-regulatory networks and identified multiple genomic sequences that are targeted by islet transcription factors that drive activity in the cells of the pancreas, according to data.
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Jorge Ferrer
“These results show how islet accessible chromatin maps can pinpoint functional cis-regulatory variants that are strong candidates for having a causal role in driving [type 2 diabetes] association signals,” the researchers wrote.
The sequences identified were found in clusters of enhancers that form into physical 3-D chromatin domains and made them less responsive to insulin, according to data.
“The cells that produce insulin appear to be programmed to behave differently in people with type 2 diabetes,” Mark McCarthy, PhD, a Wellcome Trust senior investigator at the University of Oxford, said in a press release. “This study provides some important clues to the mechanisms which are disturbed in the earliest stages of the development of type 2 diabetes, and may point the way to novel ways of treating and preventing the disease.”
Further experiments are warranted to determine which common and lower frequency genetic variants play a role in islet cells in human diabetes, researchers wrote.
Disclosure: One researcher reports being a shareholder and consultant for Endocells. All other researchers report no relevant financial disclosures.