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Nucleotides for Application in Epigenetics

Epigenetics is the study of mechanisms that induce heritable changes in gene expression without changing the DNA sequence.

The most extensively studied epigenetic mechanisms so far are DNA methylation and histone modifications that regulate gene expression by chromatin remodeling which subsequently results in increased or decreased DNA accessibility for the transcriptional machinery depending on the specific epigenetic modification pattern[1].

In addition, RNA methylation has most recently gained attention as an epigenetic modification in mammalian cells as well[2].

Several nucleotide analogs (Tab. 1) are suitable for epigenetic modification analysis. Please refer to the corresponding references for detailed application data.

Table 1: Selection guide for epigenetic modification analysis.

Epigenetic modification Nucleotides and Nucleosides References
DNA Methylation N6-Methyl-dATP
5-Formyl-2'-dC
5-Methyl-2'-dC
5-Hydroxymethyl-2'-dC
5-Aza-dCTP
5-Methyl-dCTP [3,4]
5-Hydroxymethyl-dCTP
RNA Methylation N6-Methyl-ATP [2]
2'OMe-ATP [2]
5-Methyl-CTP [5]
5-Hydroxy-UTP
4SedTTP [6]

Selected References

[1] Portela et al. (2010) Epigenetic modifications and human disease. Nature Biotechnology 28 (10):1057.
[2] Meyer et al. (2012) Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3' UTRs and near Stop Codons. Cell 149 (7):1635.
[3] Frauer et al. (2009) A versatile non-radioactive assay for DNA methyltransferase activity and DNA binding. Nucleic Acids Research 37 (3):e22.
[4] Kaito et al. (2001) Activation of the maternally preset program of apoptosis by microinjection of 5-aza-2'-deoxycytidine and 5-methyl-2'-deoxycytidine-5'-triphosphate in Xenopus laevis embryos. Development, Growth & Differentiation 43 (4):383.
[5] Karikó et al. (2005) Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA. Immunity 23:165.
[6] Hong et al. (2018) Precise Antibody-Independent m6A Identification via 4SedTTP-Involved and FTO-Assisted Strategy at Single-Nucleotide Resolution. J. Am. Chem. Soc. 140 (18):5886.