Gamete-specific methylation correlates with imprinting of the murine Xist gene.

We have investigated the potential role of DNA methylation as a regulator of imprinted Xist expression in mouse preimplantation embryos. The active paternal allele was found to be unmodified in sperm at CpG loci near the 5' end of the gene transcription unit. In contrast, on the inactive maternal allele, these same sites are initially methylated in the oocyte and then remain modified in the early embryo. In the male germ line, these methyl moieties are removed during spermatogenesis, and this occurs before the programmed reactivation of Xist in the testis. This represents a clear-cut example of a potential methylation imprinting signal that is reprogrammable and gamete derived.