Scientists from California have discovered the mechanism of suppression of the second X chromosome in female mammals The University of California Los Angeles discovered the mechanism of inactivation of the second copy of the X chromosome in women, which has remained a mystery for many years. The discovery was reported in an article published in the journal Cell.
Female mammals have two X chromosomes, that is, two sets of sex genes. Since only one X chromosome is present in the cells of males, a situation arises with uneven levels of gene expression, which can lead to various abnormalities. To prevent this from happening, there is a mechanism for dose compensation, when one X chromosome in females is completely suppressed. Until now, scientists do not know exactly how inactivation occurs, but it is known that the choice of one of the two chromosomes is carried out randomly and an important role in this is played by the RNA molecule Xist.
Xist is required to inactivate the X chromosome early in embryonic development, and interacts with hundreds of other proteins. The researchers speculated that either multiple copies of Xist completely cover the target chromosome, or RNA molecules travel from gene to gene, directly silencing them. To test these hypotheses, the scientists labeled individual RNA molecules with fluorescent labels and used ultra-high-resolution microscopy to determine their exact location on the chromosome.
It turned out that Xist are located at only 50 points on the X chromosome, which is enough to turn off (silencing) more than a thousand genes. RNA molecules attract many specialized proteins to the chromosome. When DNA is tightly packed by other proteins (Polycomb group), all genes on the X chromosome are in close proximity to the silencing points. When the researchers suppressed the Polycomb proteins, only those regions of the X chromosome that were near the Xist points were inactivated.
The results will help develop new treatments for diseases associated with dose compensation. For example, reactivation of the X chromosome may serve as a strategy for treating diseases such as Rett syndrome, which is severe mental retardation and is associated with a mutation in the MECP2 gene on the X chromosome.