DNA methylation dynamics during in vivo differentiation of blood and skin stem cells

DNA methylation is a mechanism of epigenetic regulation that is common to all vertebrates. Functional studies support its relevance for tissue homeostasis, but the global dynamics of DNA methylation during in vivo differentiation have not been worked out in detail. Here we report high-resolution DNA methylation maps of adult stem cell differentiation in mouse, focusing on 19 purified cell populations of the blood and skin lineages. Except for global demethylation in erythrocytes, observed DNA methylation changes were locus-specific and relatively modest in size. They frequently overlapped with lineage-associated transcription factors and their binding sites, suggesting that DNA methylation may protect cells from aberrant transcription factor activation. DNA methylation and gene expression provided highly complementary information, and combining the two enabled us to infer the blood lineage hierarchy directly from genomic data. In summary, our dataset and analysis demonstrate that in vivo differentiation of adult stem cells is associated with small but informative changes in the distribution of DNA methylation across the mouse genome.

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Bock C, Beerman I, Lien WH, Smith ZD, Gu H, Boyle P, Gnirke A, Fuchs E, Rossi DJ, Meissner A