The role of epigenetics in chromatin plasticity. (A) Chromatin in most primitive pluripotent stem cells (eg, embryonic stem cells) is in an open/active state (euchromatin) and several genes are transcribed. This state is due to wide undermethylation of DNA in and its association with acetylated histones that are a mark of euchromatin. (B) The cell differentiation is linked to gradual methylation of cytosine at cytosine-phosphate-guanine (CpG) dinucleotides that reside within DNA regulatory sequences affecting the gene expression. These CpG dinucleotides are gathered in the DNA strand in repetitive sequences present usually around transcription start sites (TSS) of promoters of some genes; they are called CpG islands (CGI). Whereas CGI⁺ genes encode developmental regulators or housekeeping genes, CGI⁻ genes are highly enriched for lineage-specific genes. The methylation of CpGs usually negatively affects transcription of neighboring genes. Transcription of particular genes is also affected by another epigenetic mechanism: recruitment of transcription repressive complexes by CpG-enriched DNA and posttranslational modification of histone tails that leads to a decrease in their acetylation. Thus, during the differentiation process, the open type of euchromatin changes to the more condense and genetically silent heterochromatin.