Science 3 min read

Scientists Uncover Mystery Behind the DNA Methylation Process

Image courtesy of Shutterstuck

Image courtesy of Shutterstuck

Every species marks its DNA with methyl groups in a process called DNA methylation.

Aside from regulating gene expression, DNA methylation also helps distinguish indigenous DNA from foreign ones. It also serves as a way of marking old DNA strands during replication.

Past studies have identified specific enzymes, known as methyltransferases, as responsible for methylation. They create an epigenetic layer on top of DNA by arranging the methyl group in a particular pattern.

However, scientists have not been able to identify which enzymes create which pattern, until now.

In a paper in Nature Communications, researchers from The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain) at Technical University of Denmark described how they coupled enzymes with specific methylation patterns in two bacteria.

In a statement, first author of the study and researcher at DTU Biosustain, Torbjørn Ølshøj Jensen said:

“Knowing which enzyme does what opens up to a lot of applications. With this knowledge, you can construct model organisms with artificial methylomes, mimicking the methylation pattern of the strain you want to introduce DNA to. In this way, you can ensure ‘survival’ of introduced DNA.”

The Problem With DNA Methylation

Cell factories, also known as production hosts, introduce foreign DNA into a host organism to create new things. These include medicine, sustainable bio-chemicals, and food.

Unfortunately, the process has never been easy. Scientists often experience issues with methylation when trying to introduce foreign DNA to a host organism.

The methylation pattern recognizes the DNA as an alien, causing the host to reject and chop it into pieces. E.coli seems to be one of the only exceptions.

Jensen noted:

“Working in other bacteria than E. coli, you often have to do a lot of trial and error when it comes to DNA transformation, but that’s just not good enough. You need knowledge and tools. With this, you have a systematic and rational way of fixing the problems.”

So, the researchers set out to uncover the mystery of DNA methylation by identifying which enzymes are responsible for which patterns.

Finding an Enzymes Methylation Pattern

To unravel this mystery, the researchers constructed DNA-rings (plasmids) which contain one of the methyltransferases and “cassettes” with multiple copies of specific DNA patterns.

Then, they coupled the DNA-patterns called motifs with the methyltransferases expressed by the plasmid. In turn, the pairing marked the DNA in a way that revealed the enzyme’s methylation pattern.

The researchers repeated the same process for all methyltransferases. Then, they read all the plasmids using a sequencing method that was designed to reveal methyl groups.

In the end, the DTU scientists had created a library of enzyme-to-motif couplings. They later performed some analysis to validate the method.

According to the research team, their quick method of identifying methyltransferase methylation patterns could ease other researchers’ struggle with DNA degradation.

The team also hopes to design hosts with unambiguous “methylome” that can only harbor the required methyltransferases. That way, introducing foreign DNA into non-model organisms will become easier.

Read More: Edgy Explains: What is DNA Data Storage?

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Sumbo Bello

Sumbo Bello is a creative writer who enjoys creating data-driven content for news sites. In his spare time, he plays basketball and listens to Coldplay.

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