The Xist Locus

Chromosome balance is critical for normal development. When a condition with extra or missing chromosome exists, the effects are damaging if the balance is not somehow restored. A classic example is Down’s syndrome in humans, which is characterized by trisomy 21. When the single-X male:double-X female system of sex determination evolved, survival was dependent on the co-evolution of a dosage compensation system. In Drosophila, the essence of dosage compensation is hypertranscription of the male single X chromosome, thereby producing equivalence of X-linked gene expression in males and females. In mammals, the unique feature of dosage compensation is silencing of one of the two Xs in the female to bring about equivalence of expression between male and female X chromosomes. A critical factor in the silencing of one X chromosome in the females of placental mammals is the noncoding RNA, XIST, which stands for ‘X inactive specific transcript’. XIST, the gene encoding this RNA, is the focus of this article.