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Cambridge Reproduction


De novo DNA methylases, DNMT3A and DNMT3B, are essential for development with mouse mutants being postnatally and mid-gestationally lethal, respectively. The double DNMT3A/B knockout mice show an even greater developmental delay and do not develop past E10.5. The embryos of these mice have been extensively analysed but their placentae have been broadly overlooked. Recent data from our lab has demonstrated that loss of these proteins in vivo, predictably, ablates up to 90 % of DNA methylation. However, the transcriptomic knock-on effect appears extremely mild, which is similar to previous reports in other tissues. The apparent discrepancy in loss of DNA methylation appearing not to drastically alter the transcriptome while these proteins are required for life, is intriguing. My project will be looking to disentangle this juxtaposition. I will be looking beyond the transcriptome at how DNA methylation impacts both cis- and trans-regulatory elements in the trophoblast.