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Loosen up, DNA: Leukemia gene changes genetic packaging

location of the "red-eye reporter gene" around, sometimes inserting it into a "quiet" stretch of DNA, sometimes putting it into an active area, and sometimes inserting it near the border between the two regions. The team used the gene that controls eye color to check whether a given stretch of DNA was on or not. If the fly's eyes were red, the gene was turned on; if the fly's eyes were white, the gene was turned off.

In flies with normal amounts of JAK/STAT, the eye color was predictable based on where the gene was inserted ?the gene was silent when expected, producing flies with white eyes, and active when expected, producing flies with red eyes. But in flies with increased JAK/STAT signaling, similar to what occurs in many leukemia patients, Li's team unexpectedly found that some flies that should have had white eyes had red eyes instead. The red-eye gene was sometimes active when it should have been silenced.

The research shows that JAK/STAT was able to open up the previously silent part of the genome, somehow turning on the red-eye gene by changing the gene's packaging. Genes that were previously turned off or silenced were turned on once JAK/STAT changed the genetic packaging. The team's results suggest that the pathway's ability to cause cancer is largely due to this ability; cancer-causing genes that are normally turned off become turned on once high levels of JAK/STAT open up that stretch of DNA.

Such work zeroes in on the way the body compacts a slew of genetic information into our cells while keeping the fragile DNA strands safe. Our DNA contains tens of thousands of genes along the seven feet of DNA that is spooled up very tightly around proteins called histones in the nucleus of nearly every cell in our bodies. The whole structure, called chromatin, looks much like a narrow thread wound tightly around a stack of tuna cans. While there are genes aplenty in every cell, not all our DNA is equally accessible to the cellular machin
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Source:University of Rochester Medical Center


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