Scientists have developed a new chemical technique that will significantly improve their ability to perform epigenetics research and help them understand how cells develop and function.
One of the most studied epigenetics marks is the addition of a methyl group to DNA which turns most genes off – the chemical modification is called 5-methylcytosine (5mC). Researchers from the Babraham Institute are involved in researching a DNA chemical modification called 5-hydroxymethyl-cytosine (5hmC), believed to be important for stem cell function.
Researchers believe 5hmC may be a separate epigenetic mark, or part of the process which removes methyl groups from DNA allowing genes to be switched on again. However, it was not possible to decode the epigenome – which is important to understanding how cells are regulated and how stem cells might be controlled.
A team from the University of Cambridge developed new chemistry – oxidative bisulphate sequencing or oxBS-seq – to allow 5hmC to be sequenced at single base resolution. The method was applied to sequence both 5hmC and 5mC in embryonic stem cell genomic DNA.
“Sequencing DNA is becoming an increasingly important part of science and medicine and we are pleased to have met the challenge of finding a way to sequencing this important new base modification,” said Professor Shankar Balasubramanian from Cambridge’s Chemistry department.
“There was a real need in the field for a technique that would map both 5hmC and 5mC in the genome quantitatively and at high resolution,” said Dr Miguel Branco from the Babraham Institute. “We applied this new technology to embryonic stem cells and immediately recognised its power in furthering our understanding of the biological functions of these DNA modifications.”
Professor Wolf Reik added that the new method allows researchers to map modifications with greater precision, and to relate them to stem cell function, ageing and more generally to how the environment interacts with the genome.