Dynamic methylome remodeling throughout mammalian fetal development. Mus musculus

Genetic studies have revealed an essential role for cytosine DNA methylation in gene regulation. However, its spatiotemporal distribution in the developing embryo remains obscure. Here, we profiled the DNA methylation landscape of 12 mouse tissues/organs at 8 developmental stages spanning from early embryo to birth. In-depth analysis of such spatiotemporal epigenome maps uncovered widespread regulatory DNA element dynamics during embryogenesis. We systematically delineated methylation variants that likely drive gene transcription, whose human counterparts are enriched for genetic risk factors of human diseases. Strikingly, these predicted regulatory elements predominantly lose CG methylation during fetal development, whereas the trend is reversed after birth. Key transcription factors, essential for early tissue/organ development, accumulate non-CG methylation within their gene bodies, coinciding with transcriptional repression during late stage fetal development. These spatiotemporal epigenomic datasets provide a valuable resource for studies of gene regulation during mammalian tissue/organ progression and the possible origins of human developmental diseases. Overall design: RNA-seq data (in replicate) of forebrain, midbrain, hindbrain and liver in mouse embryos from embryonic day 10.5 (E10.5) to postnatal day 0 (P0)