Methylation Research & Applications

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Although 5-methylcytosine and was discovered more than 60 years ago[1], its precise function and significance in the control of gene expression remained elusive for a further quarter of a century.

Riggs[2] and Holliday and Pugh[3] were the first to propose that methylation in mammalian DNA might have an important role in the regulation of gene expression.

Their theories provided a model for the epigenetic inheritance of a given pattern of DNA methylation, and proposed a role for DNA methylation in the specific control of gene expression in given cell types. It was also proposed to account for those cases, such as X chromosome inactivation in female eutherian mammals, where only one of two homologous genes in a diploid cell is active, whilst the other is inactive.

More recently, the role of aberrant DNA methylation in disease has been the focus of much scientific interest. It has been shown that both hyper- and hypo- methylation are common and are early events in the progression of cancers[4],[5]. In particular, aberrant methylation in many cases has been associated with the loss of expression of the so-called tumour suppressor genes. To date, hypermethylation has been associated with over a hundred genes in cancer. In addition, hypermethylation of specific genes in cancerous cells may provide excellent early markers for cancer diagnosis[6].

Genetic Signatures Ltd has invented a new DNA bisulphite modification method, which dramatically improves the yield and the efficiency of the analysis of modified DNA. The MethylEasy™ DNA Bisulphite Modification Technology has been developed as a result of this innovation.

The MethylEasy™ methodology is pivotal for understanding the roles of DNA methylation in embryonic development, gene regulation, chromatin, genomic imprinting and human diseases, especially cancer[7],[8],[9],[10],[11],[12],[13],[14]. In mammalian DNA, the main modified base is 5-mC, and occurs at a level of 2-5 % of all cytosine residues. This DNA modification predominantly occurs at cytosine residues that are located in CpG doublets[15].



[1] Hotchkiss, R.D., J. Biol. Chem., 1948, 168, 315-332.

[2] Riggs, A.D., Cytogenet. Cell Genet., 1975, 14(1), 9-25.

[3] Holliday, R., & Pugh, J.E., Science, 1975, 187(4173), 226-32.

[4] Herman, J.G., et al., Proc. Natl. Acad. Sci.USA, 1994, 91, 9700-9704.

[5] Millar, D.S., et al., Oncogene, 1999, 18, 1313-24.

[6] Millar, D.S., et al., Oncogene, 1999, 18, 1313-24.

[7] Beck, S. & Olek, A. (eds), The Epigenome, 2003, Wiley-VCH Darmstadt.

[8] Herman, J.G., & Baylin, S.B. N Engl J Med, 2003, 349.

[9] Laird, P. Nature Reviews Cancer, 2003, 3, 253-266.

[10] Cui, H., et al., Science, 2003, 299, 1753-1755.

[11] Ushijima, T., et al., Genome Research, 2003, 13, 868-874.

[12] Kriacionis, S., & Bird, A., Human Mol Gen, 2003 12, R221-R227.

[13] Klose, R., & Bird, A., Science, 2003, 302, 793-795.

[14] Paz, M.F., et al., Human Mol Genetics, 2003, 12, 2209-2219.

[15] Bird, A., Cell, 1992, 70, 5-8.