Developing female embryos have a problem males don't: instead of an X and a Y chromosome, they have two Xs and therefore, twice as many X-linked genes as they need. Scientists knew that a gene called Xist helped resolve part of the problem early on by shutting down the paternal X chromosome in a female embryo's placental material. But they didn't know what mechanism then kept the X in an inactive state. Now Terry Magnuson and colleagues from the University of North Carolina at Chapel Hill have figured it out. In the upcoming August issue of Nature Genetics, the researchers describe a gene called eed that not only keeps the brakes on paternal X chromosomes, but also plays a role in many other phases of development.
The team created female mouse embryos that lacked a copy of eed. "Without eed functioning normally, the father's chromosome is shut down and then it comes back on," Magnuson explains. "When that happens, too many X chromosome genes are active, there are problems forming placental tissue and female embryos die." Within the embryo itself, eed also appears to be involved in switching genes on or off depending on whether they're inherited from the mother or father, a key developmental process called imprinting.
"We know that this gene does other things as well," Magnuson says. "It's involved in tumor genesis. If the gene is mutated in a way that is less severe, where the protein is still produced ans still functions but not to optimal efficiency, then the animals come to term and are susceptible to developing leukemias. They also have skeletal and other problems." So too mutations in eed can result in birth defects and certain forms of mental retardation.
"We've learned from the human genome projects that there are far fewer genes than were originally estimated, roughly 35,000," Magnuson adds. "In a complex organism like humans, those 35,000 genes must act in concert with one another in many different combinations at many different times."