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DNA methylation is an epigenetic mechanism used by cells to control gene expression. A number of mechanisms exist to control gene expression in eukaryotes, but DNA methylation is a commonly used epigenetic signaling tool that can fix genes in the “off” position.

Over recent decades, scientists have made various discoveries about DNA methylation and how vital it is to a number of cellular processes such as embryonic development, X-chromosome inactivation, genomic imprinting, gene suppression, carcinogenesis and chromosome stability. Researchers have linked abnormal DNA methylation to several adverse outcomes, valtrex during pregnancy including human diseases.

DNA contains combinations of four nucleotides which include cytosine, guanine, thymine and adenine. DNA methylation refers to the addition of a methyl (CH3) group to the DNA strand itself, often to the fifth carbon atom of a cytosine ring. This conversion of cytosine bases to 5-methylcytosine is catalysed by DNA methyltransferases (DNMTs).  These modified cytosine residues usually lie next to a guanine base (CpG methylation) and the result is two methylated cytosines positioned diagonally to each other on opposite strands of DNA.

Different DNMTs work together either as de novo DNMTs, establishing the methyl group pattern on a sequence of DNA or as maintenance DNMTs that copy the methylation pattern on an existing strand of DNA to its new partner following replication. Methylation is sparse but global in mammals, found in CpG sequences across the entire genome, aside from certain stretches (of around one kilobase) where the content of CpG is high (CpG islands). When those sequences are methylated, the result can be the inappropriate silencing of genes such as tumor suppression genes.

The global distribution of methylation in mammals has posed a challenge to researchers in terms of finding out whether methylation is a default state or is targeted at specific gene sequences. However, CpG islands are generally found in close proximity to transcription start sites, suggesting there is an established recognition system.

In addition to DNA methylation being vital to healthy growth and development, it also enables the expression of retroviral genes to be suppressed, along with other potentially dangerous sequences of DNA that have entered and may damage the host.

Another important purpose of DNA methylation is the formation of the chromatin structure, which enables a single cell to grow into a complex multicellular organism made up of different tissues and organs. Scientists have established that some de novo DNMTs are components of chromatin-remodeling complexes that achieve remodeling by performing on the spot DNA methylation to fix in place the closed shape of chromatin.

DNA methylation and disease

Researchers are currently looking at the links between DNA methylation and human diseases such as lupus, cancer, muscular dystrophy and various congenital defects. Their findings could be significant in aiding the development of therapies and for understanding and preventing conditions that develop during embryonic development as a result of abnormal methylation of the X chromosome and gene imprinting.

So far, much of this research has been focused on cancer and tumor suppressor genes, since hypermethylation often results in the silencing of tumor suppressor genes in cancerous cells. Compared to normal cells, the genomes in cancer cells have also been shown to be hypomethylated over all, with hypermethylation only occurring in the genes involved in tumor cell invasion, cell cycle control, DNA repair and other processes where silencing would lead to the spread of cancer. Indeed, in colon cancer, it is possible to detect hypermethylation early on in the course of disease, meaning hypermethylation may serve as a biomarker for the condition.

Sources

  1. http://labs.genetics.ucla.edu/fan/papers/npp2012112a.pdf
  2. http://genesdev.cshlp.org/content/16/1/6
  3. http://www.sciencemag.org/content/293/5532/1068
  4. http://www.activemotif.com/documents/1654.pdf
  5. http://www.promega.com/~/media/files/
  6. www.nature.com/…/the-role-of-methylation-in-gene-expression-1070
  7. http://helicase.pbworks.com/w/page/17605615/DNA%20Methylation

Further Reading

  • All DNA Methylation Content
  • DNA Methylation: Eukaryotes versus Prokaryotes
  • DNA Methyltransferase Enzymes
  • DNA Methylation Detection
  • Epigenetics and Epigenomics
More…

Last Updated: Aug 23, 2018

Written by

Sally Robertson

Sally has a Bachelor's Degree in Biomedical Sciences (B.Sc.). She is a specialist in reviewing and summarising the latest findings across all areas of medicine covered in major, high-impact, world-leading international medical journals, international press conferences and bulletins from governmental agencies and regulatory bodies. At News-Medical, Sally generates daily news features, life science articles and interview coverage.

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