According to new research from the University of Pennsylvania, scientists have found that a clock protein known as Rev-erb is responsible for coordinating gene expression by tightening and loosening loops in chromosomes. The findings were published recently in Science.
In this study, the team found that daily oscillations of Rev-erb control gene expression in the mouse liver via interactions between on-and-off regions on the same chromosome. When the concerntraion of Rev-erb was its highest in mouse liver, cetrain genes were turned off. However, when the concerntration of Rev-erb was at its lowest, the genes that were originally turned off, were on.
The study found that Rev-erb kicks out the protein complexes that bridge the distant regions of the chromosome, thereby destabilizing the loop and turning off gene expression.
"Many studies, including this one, point to a link between the human internal clock and such metabolic disorders as obesity and diabetes," said senior author Mitchell A. Lazar, M.D., Ph.D. "Proteins such as Rev-erb are the gears of the clock and understanding their role is important for investigating these and many other diseases."
Now, the team is looking at drugs that could affect chromosome looping in cancer cells and other tissues.
Image: Schematic of Rev-erb's role in gene expression. At night (left), when Rev-erb concentration decreases, gene expression is turned on by protein complexes that loop the chromosome bringing together distant regions (blue and pink). During the day (right), when Rev-erb levels rise, the protein complexes are kicked out, causing the loop to loosen and turn off gene expression. Image courtesy of Yong Kim and Mitch Lazar, Perelman School of Medicine, University of Pennsylvania.