DNA methylation patterns of metaphase chromosomes in human preimplantation embryos.

We performed a stage-by-stage study of DNA methylation patterns in metaphase chromosomes from blastomeres of triploid and abnormal diploid human embryos. QFH-banded homologous parental chromosomes differ in their DNA methylation patterns at the metaphase of the 1st cleavage division. Chromosomes of both parental genomes are gradually demethylated at subsequent cleavages, undergoing hemimethylation in 2-cell embryos. At the 4-cell stage hypomethylated chromosomes initially appear and are further registered until the blastocyst stage. The proportion of hemimethylated and hypomethylated chromosomes varies between the blastomeres since the 4-cell stage with no preference for certain chromosomes to be hemi- or hypomethylated demonstrates random segregation of hypomethylated, undermethylated and methylated chromatids during cell cleavage. By the blastocyst stage the chromosomes acquire band- and, thus, chromosome-specific methylation patterns, with 5-methylcytosine-rich DNA preferentially accumulated in R- and T-bands and in the short arms of acrocentric chromosomes. Thus, demethylaton and remethylation of parental genomes of human embryos proceeds in the same manner from the 1st metaphase stage up to the blastocyst. These processes involve all chromosomes and all bands from each chromosome and lead to establishment of chromosome-specific DNA methylation patterns by the blastocyst stage with no differences between homologous chromosomes.