10.1093/bioinformatics/btn402

10.1016/j.cell.2007.05.009

The surface of Trypanosoma brucei, a unicellular parasite that lives in the bloodstream of its mammalian host, is coated with glycoprotein (VSG) molecules. To evade elimination by the immune system, this parasite replaces its coat with one tailored from another glycoprotein variant. Even though there are hundreds of VSG genes in the genome, this process, called antigenic variation, works because all are silenced except for the one that encodes the current coat. In this work, we show that the chromatin-modifying enzyme DOT1B helps to epigenetically regulate the number of VSGs each parasite can have at a time at the surface and how fast each parasite can switch from one coat to another. In parasites lacking DOT1B, silent VSG genes become partially active and the switch from one VSG to another slows down, allowing two different VSGs to appear on the surface of an individual parasite at the same time. Our studies reveal the importance of epigenetics in regulating VSG genes and provide new insights toward the understanding of this unique survival device.