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Mapping recently identified nucleotide variants in the genome and transcriptome

Abstract

Nucleotide variants, especially those related to epigenetic functions, provide critical regulatory information beyond simple genomic sequence, and they define cell status in higher organisms. 5-methylcytosine, which is found in DNA, was until recently the only nucleotide variant studied in terms of epigenetics in eukaryotes. However, 5-methylcytosine has turned out to be just one component of a dynamic DNA epigenetic regulatory network that also includes 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. Recently, reversible methylation of N6-methyladenosine in RNA has also been demonstrated. The discovery of these new nucleotide variants triggered an explosion of new information in the epigenetics field. This rapid research progress has benefited significantly from timely developments of new technologies that specifically recognize, enrich and sequence nucleotide modifications, as evidenced by the wide application of the bisulfite sequencing of 5-methylcytosine and very recent modifications of bisulfite sequencing to resolve 5-hydroxymethylcytosine from 5-methylcytosine with base-resolution information.

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Figure 1: DNA nucleotide variants, including 5hmC, 5fC and 5caC.
Figure 2: Summary of genome-wide, affinity-based, 5hmC-profiling methods.
Figure 3: OxBS-Seq and TAB-seq for single-base resolution sequencing of 5hmC.
Figure 4: New sequencing methods for RNA modifications.

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Acknowledgements

This study was supported by US National Institutes of Health (HG006827 to C.H.). We thank S.F. Reichard, for editing the manuscript.

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Correspondence to Chuan He.

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Song, CX., Yi, C. & He, C. Mapping recently identified nucleotide variants in the genome and transcriptome. Nat Biotechnol 30, 1107–1116 (2012). https://doi.org/10.1038/nbt.2398

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