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RNAi Epigenetics Gene Regulation

DNA Methylation

Methylation is a normally occurring modification to DNA in both eukaryotic and prokaryotic organisms. In many plants and animals, it is characterized by the biochemical addition of a methyl group (CH3) to the cytosine 5-carbon in cytosine-phosphate-guanosine (CpG) dinucleotides via a methyltransferase enzyme (Adams et. al. 2001). In plants, the cytosine can be methylated in the CpG, CpNpG, and CpNpN context, where N represents any nucleotide but guanine.

Although CpG dinucleotides occur rather infrequently in mammalian genomes (approximately one-fourth the expected frequency), DNA segments abundant with CpG dinucleotides do exist. Called CpG islands, these segments are typically 500-2000 base pair long and commonly correspond to transcription start sites. CpG dinucleotides occurring within promoters or first exons are much less likely to be methylated compared to those appearing elsewhere. DNA methylation studies have come into prominence, in part, because of expectations that CpG islands occurring in promoter regions are likely to play a regulatory role.

In higher eukaryotes DNA methylation acts as another method for the regulation of gene expression (Costello and Plass, 2001). Aberrant methylation is a widespread phenomenon in cancer and may be among the earliest changes to occur during oncogenesis (Stirzaker, et al., 1997). DNA methylation has also been shown to play a central role in gene imprinting, embryonic development, x-chromosome gene silencing, and cell cycle regulation. 

Current Topics in DNA Methylation Research

DNA Methylation Analysis Workflow

  • Since the first published article to report on bisulfite induced modification of DNA in 1992 (Frommer, et al. 1992), the bisulfite conversion technique has become a preferred tool for methylation analysis. Need help getting started? Read up on experimental workflows for bisulfite conversion.

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