Methylation of cytosine residues in the context of CpG dinucleotides within 
mammalian DNA is an epigenetic modification with profound effects on 
transcriptional regulation. A group of enzymes, the DNA methyltransferases 
(DNMTs) tightly regulate both the initiation and maintenance of these methyl 
marks. Loss of critical components of this enzymatic machinery results in 
growth, viability, and differentiation defects in both mice and humans, 
supporting the notion that this epigenetic modification is essential for proper 
development. Beyond this, DNA methylation also provides a potent epigenetic 
mechanism for cellular memory needed to silence repetitive elements and preserve 
lineage specificity over repeated cell divisions throughout adulthood. Recent 
work highlighting the specialized roles of DNA methylation and 
methyltransferases in maintaining adult somatic stem cell function suggests that 
further dissection of these mechanisms will shed new light on the complex nature 
of self-renewal.