The centre of the diagram shows levels of 5mC and 5hmC chemical modifications along a chromosome (section of DNA). The cycle illustrates that after addition to DNA, 5mC (blue) can be converted to 5hmC (red) and then subsequently removed. Image by Miguel Branco
New technique has important implications for stem cell research and the development of regenerative medicines.
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 sequence this important new base modification."
—Professor Shankar Balasubramanian FRS, of the University of Cambridge Chemistry Department and Cancer Research UK Cambridge Research Institute
Collaboration between scientists at Cambridge University and the Babraham Institute have demonstrated a new technique that will significantly improve scientists’ ability to perform epigenetics research and help unlock the door to understanding how cells develop and function. Epigenetics is a branch of genetics that studies modifications to the DNA which affect gene activity. The research has important implications for stem cell research and the development of regenerative medicines.
All the cells in the body have the same DNA sequence (genome), but it is how this DNA sequence is interpreted that results in the formation of different cell types. Epigenetic changes control how a DNA sequence is interpreted, specifically how different genes are switched on and off in different cell types, tissues and organs.
One of the most studied epigenetic marks is the addition of a very small chemical modification called a methyl group to DNA, which turns associated genes off. Methyl groups are always added to the DNA base cytosine and so this chemical modification is called 5-methylcytosine (5mC). Babraham Institute scientists are involved in researching the role of another DNA chemical modification in mammals called 5-hydroxymethyl-cytosine (5hmC), which is believed to be important for stem cell function, helping to define how the body develops. 5hmC may be a separate epigenetic mark or possibly be part of the process which removes methyl groups from DNA, allowing genes to be switched on again. Decoding the ’epigenome’ will provide greater understanding of how cells are regulated and has major implications for regenerative medicine and how cells such as stem cells can be controlled.
Professor Shankar Balasubramanian FRS, of the University of Cambridge Chemistry Department and Cancer Research UK Cambridge Research Institute, and his PhD student Michael Booth invented new chemistry to allow the recently discovered base 5hmC to be sequenced in DNA at single base resolution. This was not possible using existing methods. In a fruitful collaboration between the Cambridge group (led by Balasubramanian) and the Babraham Institute (led by Professor Wolf Reik FRS), this method was applied to sequence 5hmC and 5mC in embryonic stem cell genomic DNA.
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