Expression analysis suggests that DNMT3L is required for oocyte de novo DNA methylation only in Muridae and Cricetidae rodents
During early mammalian development, DNA methylation undergoes two waves of reprogramming, enabling transitions between somatic cells, oocyte and embryo. The first wave of de novo DNA methylation establishment occurs in the oocytes. Its molecular mechanisms has been studied in mouse, a classical mammalian model. Current dogma describes DNA methyltransferase 3A (DNMT3A) and its cofactor DNMT3L as two essential factors for oocyte DNA methylation – the ablation of either leads to nearly complete abrogation of DNA methylation. However, DNMT3L is not expressed in human oocytes, suggesting that the mechanism uncovered in mouse is not universal across mammals. We analyzed available RNA-seq datasets from oocytes of multiple mammals including our novel naked mole-rat oocytes dataset, and revealed that Dnmt3l is expressed only in the oocytes of mouse, rat and golden hamster. We identified a specific promoter sequence recognised by an oocyte transcription factor complex associated with Dnmt3l activity and demonstrated that it emerged in the rodent clade Eumuroida, comprising the families Muridae (mice, rats, gerbils) and Cricetidae (hamsters). Therefore, Dnmt3l is expressed and consequently plays a role in de novo DNA methylation only in the oocytes of these species, instead of being an essential pan-mammalian factor. Overall design: RNA-sequencing of naked mole-rat (5 replicates, natural conditions), guinea pig (1 replicate) and coruro (1 replicate) oocytes