Methylation

Embryonic development

In early development (fertilization to 8-cell stage), the eukaryotic genome is demethylated. From the 8-cell stage to the morula, de novo methylation of the genome occurs, modifying and adding epigenetic information to the genome. By blastula stage, the methylation is complete. This process is referred to as "epigenetic reprogramming". The importance of methylation was shown in knockout mutants without DNA methyltransferase. All the resulting embryos died at the morula stage.

Methylation in postnatal development

Increasing evidence is revealing a role of methylation in the interaction of environmental factors with genetic expression. Differences in maternal care during the first 6 days of life in the rat induce differential methylation patterns in some interleukin signaling have been shown to be regulated by methylation (Bird A. (Mar 2003). "Il2 transcription unleashed by active DNA demethylation.". Nature Immunology 4(3): 208-9.).

Methylation and cancer

The pattern of methylation has recently become an important topic for research. Studies have found that in normal tissue, methylation of a gene is mainly localised to the coding region, which is CpG poor. In contrast, the promoter region of the gene is unmethylated, despite a high density of CpG islands in the region.

Neoplasia is characterized by "methylation imbalance" where genome-wide hypomethylation is accompanied by localized hypermethylation and an increase in DNA methyltransferase (1). The overall methylation state in a cell might also be a precipitating factor in carcinogenesis as evidence suggests that genome-wide hypomethylation can lead to chromosome instability and increased mutation rates (3). The methylation state of some genes can be used as a biomarker for tumorigenesis. For instance, hypermethylation of the pi-class glutathione S-transferase gene (GSTP1) appears to be a promising diagnostic indicator of prostate cancer (2).

In cancer, the dynamics of genetic and epigenetic gene silencing are very different. Somatic genetic mutation leads to a block in the production of functional protein from the mutant allele. If a selective advantage is conferred to the cell, the cells expand clonally to give rise to a tumor in which all cells lack the capacity to produce protein. In contrast, epigenetically mediated gene silencing occurs gradually. It begins with a subtle decrease in transcription, fostering a decrease in protection of the CpG island from the spread of flanking heterochromatin and methylation into the island. This loss results in gradual increases of individual CpG sites, which vary between copies of the same gene in different cells (6).

Methylation and bacterial host defense

Additionally, genetic fingerprinting and genetic engineering.

Methylation in chemistry

Main article: alkylation

The term methylation in ketone.

Alternatively, the methylation may involve use of tert-butanol:

References

1. M. Nakayama, M. L. Gonzalgo, S. Yegnasubramanian, X. Lin, A. M. D. Marzo and W. G. Nelson (2004). "GSTP1 CpG island hypermethylation as a molecular biomarker for prostate cancer". Journal of Cellular Biochemistry 91 (3): 540-552. doi:10.1002/jcb.10740.
2. Grewal, S.I.; Rice, J.C. (2004). "Regulation of heterochromatin by histone methylation and small RNAs". Current Opinion in Cell Biology 16 (3): 230-238.
3. Jones, P.A.; Baylin, S.B. (2002). "The fundamental role of epigenetic events in cancer". Nature Reviews Genetics 3 (6): 415-428. doi:10.1038/nrg816.
4. Nakayama, J.; Rice, J. C.; Strahl, B. D.; Allis, C.D.; Grewal, S.I.; (2001). "Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly". Science 292 (5514): 110-113. doi:10.1126/science.1060118.
5. March, J.; Advanced Organic Chemistry, 5th ed., Wiley, New York, 2001.
6. Walsh, C.. "Chapter 5 - Protein Methylation", Posttranslational Modifications of Proteins. ISBN 0-9747077-3-2. 
7. Baylin, S.B.; Herman, J.G.; Graff, J.R.; Vertino, P.M.; Issa, J.P. (1998). "Alterations in DNA methylation: a fundamental aspect of neoplasia.". Advances in Cancer Research 72: 141-96. PMID 9338076.
8. Chen, R.Z.; Pettersson, U.; Beard, C.; Jackson-grusby, L.; Jaenisch, R. (1998). "DNA hypomethylation leads to elevated mutation rates.". Nature 395 (6697): 89-93. doi:10.1038/25779.