New characteristics of epigenetic mark revealed

Scientists at the Hubrecht Institute and UMC Utrecht have developed a new method to detect the DNA modification 5-hydroxymethylcytosine in single cells revealing novel characteristics about this epigenetic mark. The study is published in Nature Biotechnology this week.

The function of DNA can be modified by the addition of chemical groups. One such modification, called 5-hydroxymethylcytosine (5hmC), has been discovered recently with little known about the biological function of this epigenetic mark. Scientists at the Hubrecht Institute and UMC Utrecht, led by director Alexander van Oudenaarden, have developed a technique to determine 5hmC in single cells.

By detecting 5hmC in single cells the scientists have been able to show that the amount of 5hmC can be heavily skewed towards either the plus or the minus strand of a chromosome. This could be explained by the lack of mechanisms to copy 5hmC to the new strand after DNA synthesis. This skewed 5hmC profile allowed the researchers to create a model to infer the rates of 5hmC addition and removal. Finally, the fact that after replication and cell division the two sister cells each receive chromosomes with 5hmC on opposite strands, allowed the researchers to predict if cells are sister cells or even cousins.

Cell identity is controlled and maintained by DNA methylation. Disruption of these marks can lead to developmental defects and cancer. 5hmC can potentially be used as a unique and endogenous label to identify sister cells, thereby allowing researchers to understand the lineage relationship of cells not amendable to invasive labeling strategies, such as human primary tissues. Knowing if two very different appearing cells come from the same mother cell can lead to new insights towards understanding the origin of cells and differentiation.

Online article