Second, we studied DNA methylation changes associated with breast epithelia differentiation44. Ectoderm to breast epithelia differentiation was dominated by DNA methylation loss (1.3M CpGs lost methylation vs. 0.2M gained), consistent with other primary somatic cell types50. Distinguishing luminal vs. myoepithelial cells by flow sorting, and comparing a set of DMRs (Table S4d) defined specifically in epithelial lineages44, we found differences in nearest-gene enrichments54 (mammary gland epithelium development vs. actin filament bundle, respectively), and differences in motif density (luminal DMRs show greater motif density for 51 TFs and lower for 0 TFs). Proximal DMRs were highly associated with increased transcription, consistent with regulatory element de-repression associated with DNA methylation loss.
