Imprinting and X-chromosome inactivation.

Abstract

In normal female mammals one of the two X-chromosomes in every somatic cell is inactive i.e. it fails to transcribe RNA (reviews Gartler et al. 1992; Migeon 1994; Lyon 1996). The result of this is that chromosomally XX females and XY males both effectively have a single dosage of the products of X-linked genes. Thus X-chromosome inactivation fulfils the function of dosage compensation of X-linked genes. In eutherian mammals, typically either one of the two X-chromosomes in any cell, the maternally inherited Xm or the paternally inherited Xp, can be inactivated at random. Once the choice is made in each cell, it remains stable in all further cell generations in that individual and hence in the adult there are large clumps of cells with the same X-chromosome active. If the two X-chromosomes bear different alleles of a gene affecting some visible character, such as coat color, the clumps can be seen as a variegated effect. The best-known example of this is the tortoiseshell cat, in which the pattern results from the animal having a gene for ginger coat on one X-chromosome and black or tabby on the other. However, by contrast, in marsupials the same X-chromosome, the paternally derived Xp, becomes inactive in all cells (Cooper et al. 1993; Graves 1996). This preferential inactivation of Xp is seen also in some cells of the extraembryonic lineages of the embryo, which give rise to the placenta and other supporting tissues, in mice and rats (Takagi and Sasaki 1975), and probably, but less clearly, in humans also (Harrison 1989; Goto et al. 1997). Thus, in marsupials and in extraembryonic tissues of eutherians, the X-chromosome shows imprinting (Fig. 1). This imprinting has some similarities and some differences from autosomal imprinting. In order to understand the significance of imprinting in X-chromosome inactivation one must consider the mechanism by which the inactivation is brought about.