Epigenetics: Fixing the dents

Epigenetics are changes in an organism that are caused by the modification of how a gene is expressed, rather than the alteration of the genetic code itself. The most common epigenetic modification is DNA methylation, where chemical tags called methyl groups are attached to the DNA, making the genetic code harder to read and be translated into proteins.

Unmethylated regions of the genome, which are known as CpG islands, are found close to promoter regions — i.e., the point where the cell machinery starts to read the gene. Although CpG islands have lots of potential methylation sites, under normal conditions, they avoid methylation. 

Some disorders, however, can result from improper methylation, especially in these regions.

Thus, to better develop model systems that can study the role epigenetics play in disease, a team of researchers, including Mo Li and Reyna Hernández-Benítez of the King Abdullah University of Science and Technology (KAUST), developed a new molecular tool to insert CpG-free DNA into a targeted region.

The team first applied this technology to model aberrant methylation in a colon cancer gene.

Next, they used the tool to add the missing methyl tags from the genome in neuronal cells derived from a patient with Angelman syndrome, restoring the level of UBE3A protein, which plays an important role in tagging damaged and unnecessary proteins for degradation.

Li and Hernández-Benítez say that, in the future, targeted epigenome editing will be a standard lab tool. Li hopes to “explore the possibility of using similar epigenome editing tools to regulate therapeutic genes to compensate for genetic defects in diseases, such as sickle cell disease, which is quite prevalent in Saudi Arabia.” 

Hernández-Benítez adds that this tool may open new avenues to explain the role aberrant DNA methylation plays in ischemic heart disease and cerebrovascular diseases — both primary causes of morbidity in the Middle Eastern region.

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