Epigenetics is the study of modifications to DNA which affect the activity of genes. DNA is normally made up of four bases – cytosine, guanine, adenine and thymine. However, these can undergo chemical modification to make new bases. Changing one of the bases in a strand of DNA in this way alters its property and function by controlling how the sequence is interpreted. This affects how genes are switched on and off in different cell types, tissues and organs.

The modified base 5-methylcytosine (5mC) is well-known epigenetic mark that can regulate transcription of the genome. Since 2009 three further modified bases have been detected in the mammalian genome. These are the TET-enzyme generated bases; 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). The presence of these modifications opens up questions as to their function in normal cellular biology and disease states.

We are developing tools to better locate and study the function of these modified bases using of state of the art genomics facilities. We have already created a method to quantitatively sequence both 5mC and 5hmC at single-base resolution. This tool will allow much more accurate study of these two epigenetic marks.

Work within the group continues to focus on identification, mapping and elucidation of the biological function of epigenetic base modifications.

References:

Quantitative Sequencing of 5-Methylcytosine and 5-Hydroxymethylcytosine at Single-Base Resolution
M J Booth; M R Branco; G Ficz; D Oxley; F Krueger; W Reik; S Balasubramanian
Science, 336 934-7 (2012)
DOI: 10.1126/science.1220671
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