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Just in time for Valentine's Day: UNC researchers identify a gene critical for heart function
Date:2/4/2011

CHAPEL HILL, N.C. Everyone knows chocolate is critical to a happy Valentine's Day. Now scientists are one step closer to knowing what makes a heart happy the rest of the year.

It's a gene called DOT1L, and if you don't have enough of the DOT1L enzyme, you could be at risk for some types of heart disease. These findings from a study led by researchers at the University of North Carolina at Chapel Hill School of Medicine appear in the Feb. 1, 2011 issue of the journal Genes and Development.

The team created a special line of mice that were genetically predisposed to dilated cardiomyopathy, a condition in which the heart expands like a balloon, causing its walls to thin and its pumping ability to weaken. About one in three cases of congestive heart failure is due to dilated cardiomyopathy, a condition that also occurs in children.

These mice lack DOT1L. The big discovery came when the researchers were able to prevent the mice from developing the disease by re-expressing a single downstream target gene, Dystrophin.

"We saw this phenotype in the heart and it could be attributed to anywhere between 1 and 1,000 genes. But when we just added back this one gene, the heart function was completely rescued," said the study's lead author, Anh Nguyen, a graduate student in the lab of biochemist Yi Zhang, PhD, at UNC's Lineberger Comprehensive Cancer Center. "It was very surprising to us," Nguyen added. "Normally you'd think you'd have to add in a number of genes to really see that effect."

The researchers discovered that the gene depends on the enzyme DOT1L to activate it. If DOT1L levels fall too low, Dystrophin ceases to perform its function, eventually leading to heart disease.

"We've identified a new function of DOT1L, which has been linked to leukemia before, but never linked to heart defects," said Zhang, Kenan Distinguished Professor of biochemistry and biophysics and an Investigator of the Howard Hug
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Contact: Les Lang
llang@med.unc.edu
919-966-9366
University of North Carolina School of Medicine
Source:Eurekalert  

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