Detecting and editing DNA methylation in oocytes

Detecting and editing DNA methylation in oocytes

Some mammalian diseases result from abnormal methylation of oocyte DNA. By modifying a technique called bisulfite sequencing, which is used to detect methylation of specific nucleotides, researchers measured site-specific DNA methylation in individual mouse oocytes and their associated first polar bodies (PB1).

PB1 is a genetic sibling of the oocyte formed during meiosis but is not required for subsequent development. Although methylation patterns differed among oocytes from the same mother, each PB1 had a methylation pattern similar to that of its associated oocyte.

The authors showed that methylation status of specific DNA sites in PB1 could predict the methylation of the same sites in the oocyte, and hence predict offspring phenotype.

Next, the authors developed a method to alter methylation patterns in individual mouse oocytes using an inactive Cas9 enzyme fused to DNA methylating or demethylating enzymes. Using this method, the authors altered the coat color of offspring, generate bimaternal embryos that developed to full term, and corrected familial Angelman syndrome, which results from incorrect methylation of maternal DNA, in a mouse model.

The results suggest a strategy for preventing or correcting maternally inherited DNA methylation disorders and may facilitate the study of maternally transmitted epigenetic information, according to the authors.