lyonization

Lyonization, also called X-chromosome inactivation, is the process by which one of the two X chromosomes in female mammals is transcriptionally silenced to balance gene expression with males who have one X chromosome. The phenomenon is named after Mary F. Lyon, who proposed the mechanism in 1961.

In early embryonic development, one X chromosome is randomly chosen in each cell to become the inactive X; the choice is maintained in all descendant cells, resulting in mosaic tissue where some cells express genes from the maternal X and others from the paternal X. The inactive X forms a Barr body, a densely stained structure in the nucleus. Inactivation is initiated at the X-inactivation center, where the XIST gene produces a long noncoding RNA that coats the future inactive X and triggers silencing. Epigenetic changes such as DNA methylation and histone modifications (for example, H3K27me3) convert the chromosome to a transcriptionally silent heterochromatin state.

Most X-linked genes are silenced on the inactive chromosome, though a subset escape inactivation and remain expressed from both Xs, contributing to variable expression among tissues. The mosaic pattern of expression explains why female carriers of X-linked disorders often have milder or variable symptoms and, in some cases, why phenotypes can be mosaic (for example, calico cats with coat color determined by X inactivation). Skewed lyonization, where one X is preferentially inactivated, can influence disease severity in females with X-linked disorders.

While random lyonization is characteristic of placental mammals, other vertebrates show different patterns, such as imprinted paternal inactivation in marsupials. Lyonization is a central mechanism of X chromosome dosage compensation in mammals.