These are exciting times not only for genomics, but also for epigenomics, the study of heritable information that is not encoded in the primary sequence of the DNA itself, but rather in the associated post-synthetic modifications to the DNA and to the histones which package it. With personalised genomics becoming increasingly possible in the era of the $1000 genome, many are beginning to look at epigenetic contributors to disease. While assessing chromatin alterations is still relatively expensive to do and difficult to standardise, DNA methylation lends itself well to next-generation sequencing techniques and highly-reproducible results can be obtained from limited patient material. The study of DNA methylation is one of the oldest branches of epigenetics and methylation is known to be crucial in such diverse processes as X-inactivation, imprinting, repeat stability and restriction of selfish elements. Methylation in mammals is largely present at cytosine in the form of 5methylcytosine (5mC) and the addition of this mark was long thought to be an irreversible process which could be removed only by replicating DNA in the absence of the methyltransferase. Recently this area has been reinvigorated by the discovery that an oxidised form of 5mC, called 5-hydroxymethylation (5hmC), is relatively abundant in embryonic stem cells, as well as in the adult brain. 5mC can be oxidised to 5hmC by the TET family of enzymes (first identified in leukemias), which may represent the first stage in the active removal of 5mC, or alternatively may represent a stable epigenetic mark in itself.
- DNA demethylation