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Epigenetics

DNA Methylation

One of the fastest growing fields in biology and cancer research is epigenetics. While the underlying genetic code defines which proteins and gene products are synthesized, it is epigenetic control that defines when and where they are expressed. This dynamic control of gene expression is essential for X chromosome inactivation, embryogenesis, cellular differentiation and appears integral to memory formation and synaptic plasticity.

Epigenetic control is generally mediated by methylation of cytidine to 5-methyl-dC in CpG sites and post-translational modification of histones. Methylation of CpG sites near promoters is associated with gene silencing, as is deacetylation of histones. A number of diseases can result when CpG methylation control is lost or when the de novo methylation is incorrect, such as Rett, Fragile X, ATR-X, Prader-Willi and Angelman syndromes. In addition, dysregulated methylation patterns are often seen in cancers and this is widely thought to contribute to tumorigenesis.

While a number of mammalian DNA methyltransferases are known in the DNMT family, the enzymes responsible for demethylation in mammals have yet to be identified conclusively since none has shown clear activity in vitro. However, recent work by the Heintz Lab. demonstrated that 40% of the purported 5-methyl-dC in Purkinje neurons was actually 5-hydroxymethyl-dC. This hydroxymethyl cytidine analog has low affinity for the Methyl-CpG-binding Protein MeCP2, which is a known transcriptional repressor, as well as DNMT1, which is the maintenance DNA methyltransferase. This opens up the possibility that demethylation would be acquired passively over multiple cell cycles if a means could be found to convert 5-methyl-dC to 5-hydroxymethyl-dC. Less than a month after Kriaucionis’ publication, the Rao Lab. found an enzyme, TET1, which catalyzes the conversion of 5-methyl-dC to 5-hydroxymethyl-dC in vitro and in vivo, ushering in a new chapter in the field of epigenetics with 5-hydroxymethyl-dC taking center stage.

Item Catalog No. Pack Price ($)
10-1062-9550 µmole335.00
10-1062-90100 µmole650.00
10-1062-020.25g1675.00

See Also

5-Me-dC      Page 43

 

OTHER INSTRUMENT TYPES

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