Figure 2.

Schematic representation of DNA methylation status surrounding a self-renewal gene (left) or a tissue lineage-specific gene (right) in pluripotent stem cells (A), in the lineage in which the gene is expressed (B) and in an alternative lineage is which the gene is silent (C). Arrows indicate the transcription start sites (TSSs). Raised circles denote CpG sites. Black filled circles are 5-methylcytosine, grey filled circles are hydroxymethylcytosine and white dots circles are unmethylated cytosine. Promoters depicted are high CpG-content promoters (HCP) (left) typical of pluripotency genes (as well as germline-specific and X-inactivated genes) and intermediate or weak CpG –island promoters (right). Most HCP of housekeeping genes and silent but “poised” developmental regulators (not shown) remain unmethylated regardless of transcriptional states. In contrast, weak CpG island promoters are preferential targets for de novo methylation in somatic cells[33]. Gene silencing may result from lack of activators or alternative repressive mechanisms independent of DNA methylation.