X-chromosome inactivation

Female mammals carry two X chromosomes, while males carry one. To avoid producing a double dose of X-linked gene products in females, each cell switches off one of its two X chromosomes. X-chromosome inactivation is this large-scale, lifelong silencing of an entire chromosome.

Early in female development, each cell randomly chooses one X to inactivate. The chosen chromosome is coated by a non-coding RNA and progressively packed into dense, silent chromatin marked by DNA methylation and repressive histone modifications. Once a cell makes the choice, all of its descendants keep the same X switched off.

Because the choice is random and then inherited by daughter cells, a female body is a mosaic: patches of cells express the maternal X and other patches express the paternal X. This is a textbook example of dosage compensation, the balancing of gene output between the sexes.

Inactivation is not absolute. A subset of genes escapes silencing and stays active on both X chromosomes, which contributes to differences seen in conditions where the number of X chromosomes is abnormal.