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Thursday, May 3, 2012

Sequencing epigenetic changes

We all inherit our genes from our parents. However, it is now known that the simple DNA sequence with which we were born tells us little about how those genes are expressed. Epigenetic (non-sequential) changes play a huge role in how genes are regulated.

The most common type of epigenetic change is the methylation of specific cytosine bases. Thanks to the efforts of Shankar Balasubramanian and his colleagues from the University of Cambridge and from the Babraham Institute, there is now a way to see exactly where these methylation changes occur.

A methyl group is simply a carbon atom attached to three hydrogen atoms. The carbon atom can form a fourth bond to whatever is being methylated, in this case a cytosine. The result is 5-Methylcytosine (5mC) (shown to the left). Highly methylated regions of the genome are associated with lower levels of gene expression. Therefore, finding these regions can tell us a lot about which genes are turned on.

Briefly, the researchers found that they could change 5mC into uracil in a series of steps by the addition of specific enzymes. By using different reagents to sequence the same strand of DNA, the could distinguish which bases had originally been 5mC. 

Why is this so exciting? As I mentioned, gene expression is tightly linked to epigenetic changes. Unfortunately, ordinary DNA sequencing cannot detect these changes. Imagine being able to determine which genes were turned off in a cell you just pulled out of a specific organ. Or being able to compare epigenetic changes before and after administering a drug. We would be able to follow gene expression under all kinds of conditions. I expect a great many uses to come from this new technique.