X-chromosome regulation in oogenesis and early mammalian development

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Abstract
Introduction The X chromosome in placental mammals is subject to a unique system of developmental regulation. This regulation involves coordinate activation and inactivation of the entire chromosome during the course of female development. The inactivation event occurs during early embryogenesis, and, once established, the inactive condition is somatically heritable in a cell lineage. The inactivation event in the embryonic lineages typically occurs at random with respect to the parental origin of X chromosomes such that the developing embryo and resulting adult is a mosaic with respect to X-chromosome expression. The primordial germ cells of the developing fetus appear to be similar to somatic cells with respect to single active X expression, and the mature X is reactivated in oogonial stages prior to the onset of meiotic prophase. The molecular mechanisms involved in the onset of inactivation and the maintenance of inactive X chromosomes are not well established, but there is an increasing amount of evidence that DNA modification, probably in the form of cytosine methylation, is involved. Moreover, there is ample evidence to suggest that DNA methylation is also associated with changes in chromatin structure and that the critical methylation changes in the inactive X chromosome occur in gene promoter regions and other regulatory sites (Wolf and Migeon 1985). This review is primarily concerned with the elements of X-chromosome regulation that take place in the early embryo.

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