X-chromosome activity: impact of imprinting and chromatin structure

The analysis of the imprinting of the X chromosome has provided insight into factors that affect the initiation and the choice of the chromosome for inactivation in the early mammalian embryo (Lyon, 1996). There are significant differences in the chromatin configuration, methylation and gene expression between Xi and Xa in somatic cells. Preferential paternal X inactivation that is concomitant with widespread heterochromatinization first occurs in the trophectoderm in the blastocyst. It is now clear that the activity of some paternal X-linked genes are suppressed before this stage. In the epiblast there may be early preferential paternal X inactivation before a random pattern supersedes. These observations suggest that parent-specific modification of the chromosome may determine the choice of which X chromosome is to be inactivated (Lyon, 1996). Differential methylation within the Xist gene or the XIC may lead to imprinted X-chromosome behavior. Alternatively, we postulate that imprinting of the X chromosome may be related to differences in chromatin configuration of the X chromosome in male and female germ cells which may then influence X-linked gene expression in the early embryo (Fig. 4). This may occur with a gene by gene effect leading to suppression of paternal alleles. An overall chromatin difference in the chromosomes may influence imprinted paternal Xist expression in early embryos and in the trophectoderm and primary endoderm populations that segregate early from the totipotent progenitors. Alternatively more specific differences in the chromatin architecture of the Xist gene or other gene loci in the Xic may constitute the signature of the imprint.