Cancer epigenetics takes center stage

Epigenetics is defined as modifications of the genome, heritable during cell division, that do not involve a change in the DNA sequence. Examples include methylation induced premeiotically in Ascobolus, repeat-induced gene silencing and paramutation in plants, mating type silencing and telomere silencing in yeast, position effect variegation in Drosophila, and genomic imprinting in mammals and flowering plants. There are several features that distinguish epigenetics from conventional genetic mechanisms: reversibility; position effects, i.e., the ability to act over unexpected distances larger than a single gene; apparent mutations at unexpectedly high frequency; and the involvement of gene domains. One common thread to most epigenetic phenomena is DNA methylation, a covalent modification of the C5 position of cytosine. This methylation pattern is stably maintained at CpG dinucleotides by a family of DNA methyltransferases that recognize hemimethylated CpG dinucleotides after DNA replication. DNA methyltransferases belong to multiprotein complexes, and they contain sequence motifs for multiple such interactions, including interactions with chromatin components, some of which have been directly identified (3). Another common thread to epigenetics is a link to transcriptional regulation, generally involving gene silencing. DNA methylation in particular is generally but not exclusively linked to transcriptional silencing, including methylation induced premeiotically, paramutation, and mammalian gene silencing.