Correct establishment of DNA methylation patterns is essential in development and required for silencing retrotransposons. In 2010, we published one of the largest databases of human DNA methylation data at that point (Edwards et al. 2010). Analyses of this data supported the hypothesis that the entire genome, including all transposable elements, was targeted for methylation, but that certain regions such as CpG islands were protected from this mechanism likely by histone modifications. More recent work as identified the protein Fbxl10 as being critical for the protection of a subset of CpG islands from methylation (Boulard et al 2015, 2016) and a role for OGT in mediating methylation-based repression of retrotransposons (Boulard et al. 2020).