Although epigenetics is formally defined as a heritable change in gene expression or chromosomal stability by utilising DNA methylation, covalent modification of histones and non-coding RNAs without a change in DNA sequence, it is increasingly used to define long term changes that alter the physiology of a subset of cells in a tissue. Epigenetic changes are common in diseases such as cancer, and understanding the mechanisms responsible for these aberrant epigenetic changes will allow treatment that can inhibit adverse affects.
DNA methylation occurs with transcriptional consequences predominantly on cytosines of the dinucleotide CpG clusters called CpG islands that are found close to the start points of transcription. Cancer cells often show transcriptional repression of tumour suppressor genes through hypermethylation of CpG islands. Recent developments have shown that the processes related to DNA methylation are more dynamic than had been appreciated previously. Using cells synchronised by different methods, we have shown that the methyl groups on the DNA at the promoter region of ten genes cycle that imply a demethylation step. Subsequently it was shown that there are further modifications to the methyl group with hydroxyl methylated DNA becoming a new component of the DNA modification cycle. These results point to new opportunities to influence gene expression at key gene loci in cancers and other diseases. Chromatin remodeling is by the so called “histone-code” involving various covalent modifications of the histones, and has been subject to very many studies and their importance is now very well accepted. However, the transcriptional state can also be regulated by many chromatin-associated protein complexes that are either involved in enhancing or fine-tuning of the promoter activity and, of course some of these respond to the altered contexts that arise from the histone and DNA modifications. We will focus on novel aspects of the histone methylation status and related “off-target” activities of the enzymes involved.