DNA METHYLATION PATTERNS AND SEQUENCE TRANSITIONS OF THE CPG ISLAND OF MOUSE HPRT DURING EARLY EMBRYOGENESIS

The timing and pattern of methylation of the CpG island in the X-chrom osome gene, Hprt, was examined using bisulfite methods to assess the o ccurrence of DNA cytosine methylation at the onset of X-chromosome ina ctivation (XCI). The Hprt sequences were extensively methylated in 4.5 dpc blastocysts, and the levels of methylation progressively decrease d to 7.5 dpc. Adult patterns of methylation were established in the em bryonic tissues after 7.5 dpc. By contrast, methylation continued to d ecrease in extraembryonic lineages and at 13.5 days was not detectable on the paternal Hprt sequences in the yolk sac endoderm. In the bisul fite-treated coding strand, numerous G to A transitions and CpTpG meth yaltions were observed that were unique to the methylated or nonmethyl ated Hprt sequences, respectively, in early development.