ABSTRACT

The establishment and maintenance of patterns of gene expression involve chromatin modifications that often are equaled to epigenetic marks. Polycomb gene (PcG) products assemble into chromatin-associated multiprotein complexes with a role in transcriptional repression. The interplay between PcG products and DNA methylation is further underlined by the increased likelihood of PcG target genes being methylated in tumor cells compared to that of nontargets. The association of PcG regulation to developmental processes reflects their suitability as a flexible, dynamic system for transcriptional regulation of a subset of genes with roles in the determination of cell states and transitions between them. In mammals, DNA methylation is restricted to the cytosine–guanine (CpG) dinucleotide, which is underrepresented except for short sequence stretches called CpG islands, often associated with promoters. Abnormal DNA methylation patterns, in which sequences at some loci hypomethylated whereas at others, including tumor suppressor genes, they hypermethylated and were transcriptionally inactivated, are a feature of tumor cells and neoplasms.