DNA methylation at cytosines is a crucial mechanism in the spatiotemporal regulation of gene activity, for example by directly affecting the binding of transcription factors to target regulatory elements. As part of the third phase of ENCODE, He and co-workers1 have performed whole-genome bisulfite sequencing to provide methylome maps for twelve tissue types, representing the three primordial germ layers, at nine developmental stages in mouse between embryonic day 10.5 (E10.5) and birth, with data for some tissues collected into adulthood. Fetal tissues showed high levels of CpG methylation; this was progressively lost through embryonic stages until birth, after which many regions were re-methylated. Only 8.5% (153,019) of the 1,808,810 CpG regions that were differentially methylated between tissue types and developmental stages were located in promoters, CpG islands (CGIs) and CGI shores. Many of the remaining 91.5% were inferred to locate to fetal enhancers (fetal enhancer differentially methylated regions, or feDMRs). Non-CpG methylation (mCH, where H is A, C or T) was found to accumulate in large genomic, mostly intragenic, regions and to be associated with repression of early fetal developmental pathways. By intersecting feDMRs with genetic variant information from human genome-wide association studies, the authors showed that SNP-based heritability for human traits and diseases was enriched in regions orthologous to mouse feDMRs, highlighting the value of this dataset for a better understanding of the role of potential regulatory elements in mammalian development and disease.