DNA methylation

DNA methylation is a special process in living things where tiny methyl groups stick to the DNA. This doesn’t change the order of the letters in the DNA, but it can turn genes on or off. When methylation happens in a special part of a gene called a gene promoter, it usually stops that gene from working, a process called repressing gene transcription.

In animals, DNA methylation is very important for growing normally. It helps with things like genomic imprinting, where some genes work differently depending on if they come from the mother or the father. It also helps with X-chromosome inactivation, making sure that females, who have two X chromosomes, only use one in each cell. DNA methylation also keeps jumping pieces of DNA called transposable elements in place. It plays a role in aging and can be linked to health problems like cancer.

Scientists have found that DNA methylation usually happens on two types of building blocks in DNA: adenine and cytosine. Cytosine methylation is common in many living things, from plants to animals, though the amount can change a lot between different species. This process helps keep DNA stable and accurate when it makes copies of itself.

Conserved function of DNA methylation

DNA methylation is a process where tiny chemical groups are added to DNA. This can change how genes work without changing the DNA sequence itself.

In animals, most DNA is usually methylated. In plants and other organisms, the pattern is more mixed.

One important role of DNA methylation is to keep certain genes turned off. It can also stop pieces of DNA called "transposable elements" from moving around. This helps keep the genome stable. In highly active genes, methylation can also help with reading the gene correctly.

In mammals

DNA methylation patterns change a lot between generations in mammals. Most methylations from parents are removed during the formation of eggs and sperm, and again early in embryo development. After this, new methylation happens when the embryo implants, helping control which genes are active in different cells. These patterns stay the same for a long time, helping each cell type stay unique.

DNA methylation helps keep certain genes turned off, especially in cells that have finished developing. It is important for keeping genes quiet depending on which parent the gene came from, and for turning off one of the two X chromosomes in females. Without DNA methylation, many specialized cells cannot survive. However, in early stem cells, DNA methylation is not needed.

DNA methyltransferases (in mammals)

DNA methylation in mammals mainly happens at a special spot in DNA called CpG dinucleotides. There are two main types of enzymes that add methyl groups to DNA: ones that keep existing methylation patterns and ones that create new ones.

One enzyme, DNMT1, helps keep methylation patterns the same when cells copy their DNA. Another group of enzymes, including DNMT3A and DNMT3B, sets up new methylation patterns early in development. There are also special proteins that help these enzymes work better.

In plants

We have learned a lot about DNA methylation using a small plant called Arabidopsis thaliana. In plants, DNA methylation works a bit differently than in animals. While animals mostly add methyl groups to a specific part of the DNA called a CpG site, plants can add them to several different places.

Scientists have found enzymes in plants, such as DRM2, MET1, and CMT3, that add these methyl groups to DNA. These enzymes help control which genes are active and which are turned off. They also help protect the plant’s DNA from harmful changes. Different plants have different levels of DNA methylation, with some having much more than others.

In insects

Further information: Epigenetics in insects

Insects have different amounts of DNA methylation in their bodies. Butterflies have small amounts, while some bugs and cockroaches have more, up to 14% in certain parts of their DNA. In honey bees, DNA methylation helps control genes by marking parts of them.

Fruit flies, called Drosophila melanogaster, have very little DNA methylation, about 0.1–0.3% of their DNA. New research shows even smaller amounts of another type of methylation when they are very young.

In fungi

Many fungi have a special change called DNA methylation. This change can affect how genes work. The amount of this change is different in different types of fungi. Some fungi have very little, while others have more.

Some tiny fungi, like brewers' yeast and fission yeast, do not have DNA methylation at all. But a type of fungus called Neurospora crassa does have a system for DNA methylation. Scientists study this fungus to learn more about how DNA methylation works. Changing the genes that control this process does not stop the fungus from growing or reproducing.

In other eukaryotes

DNA methylation is not often found in Dictyostelium discoideum. It happens in only a very small part of its DNA. But it is more common in Physarum polycephalum, where it can be in up to 8% of the DNA. This shows that DNA methylation can be different in different organisms.

In bacteria

Adenine or cytosine methylation in bacteria is managed by special systems that help protect the bacteria from viruses. These systems use enzymes called methylases to add methyl groups to specific parts of the DNA. This marking helps the bacteria recognize their own DNA.

In E. coli, a specific enzyme called DNA adenine methyltransferase (Dam) adds methyl groups to a sequence called GATC. This process is important for fixing mistakes in DNA, controlling when DNA copies itself, and turning genes on or off. The methylation helps the cell know which part of the DNA is the original and which is the new copy. Certain genes depend on this methylation to turn on or off based on the bacteria's environment.

Detection

DNA methylation can be found using many different scientific methods. One common way is Mass spectrometry. This can detect methylation but does not show where it is in the DNA.

Another method is Methylation-Specific PCR (MSP). It uses a special chemical to change parts of DNA that are not methylated. This makes it easy to see if a section is methylated.

Other techniques include Whole genome bisulfite sequencing. This looks at the entire genome after treating DNA with a chemical that changes unmethylated parts. There are also methods like Enzymatic methyl-seq (EM-seq), which uses enzymes to find unmethylated areas. Scientists also use the HELP assay, which uses special enzymes to tell if DNA is methylated. They also use Pyrosequencing and Illumina Methylation Assay to measure methylation levels. These tools help researchers learn how DNA methylation affects genes and health.

Differentially methylated regions (DMRs)

Differentially methylated regions (DMRs) are parts of DNA that have different patterns of methylation in different samples, such as tissues or cells. These regions help control which genes are active.

There are different types of DMRs, such as those found between cancer and normal cells, or those that change during development or with age. Researchers use tools to measure and identify these regions, helping us learn how DNA methylation affects health.

DNA methylation marks

DNA methylation marks are special chemical tags added to DNA in our cells. These tags help control which genes are active. They influence how cells behave and what they can do. Scientists study these tags to learn how cells develop and stay specialized.

DNA methylation can also help identify tiny amounts of body fluids, like blood or saliva. Researchers can tell what kind of fluid is present by looking at methylation patterns, even in very small or old samples. This makes it a useful tool for solving crimes and monitoring some diseases.

Computational prediction

DNA methylation can be studied using computer programs and special methods. These programs help scientists learn where methylation happens on chromosomes. They are often faster and cheaper than lab experiments. Some of these new methods come from researchers like Bhasin, Bock, and Zheng. Using both computer models and lab experiments helps scientists understand DNA methylation better.