image: Yellow mice generated by targeted DNA demethylation in oocytes derived from pseudoagouti mothers. view more
Credit: Image courtesy of Yanchang Wei.
Researchers report a method for 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, Yanchang Wei and colleagues 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 the 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 DNA-demethylating enzymes. Using this method, the authors altered the coat color of offspring, generated bi-maternal 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.
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Article #18-17703: "DNA methylation analysis and editing in single mammalian oocytes," by Yanchang Wei et al.
MEDIA CONTACT: Yanchang Wei, Shanghai Jiao Tong University, CHINA; tel: +86-021-20284520, +86-15210722864; e-mail: <weiyc@shsmu.edu.cn>
Journal
Proceedings of the National Academy of Sciences