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Charting oxidized methylcytosines at base resolution.

ABSTRACT: DNA cytosine methylation is a key epigenetic mark that is required for normal mammalian development. Iterative oxidation of 5-methylcytosine (5mC) by the TET family of DNA dioxygenases generates three oxidized nucleotides: 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Recent advances in genomic mapping techniques have suggested that these oxidized cytosines not only function in the process of active reversal of 5mC but also may possess unique regulatory functions in the mammalian genome.

SUBMITTER: Wu H

PROVIDER: S-EPMC4671372 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Charting oxidized methylcytosines at base resolution.

Wu Hao H Zhang Yi Y

Nature structural & molecular biology 20150901 9

DNA cytosine methylation is a key epigenetic mark that is required for normal mammalian development. Iterative oxidation of 5-methylcytosine (5mC) by the TET family of DNA dioxygenases generates three oxidized nucleotides: 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Recent advances in genomic mapping techniques have suggested that these oxidized cytosines not only function in the process of active reversal of 5mC but also may possess unique regulatory fu ...[more]

PMID: 26333715

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Simultaneous sequencing of oxidized methylcytosines produced by TET/JBP dioxygenases in Coprinopsis cinerea.

Project description:TET/JBP enzymes oxidize 5-methylpyrimidines in DNA. In mammals, the oxidized methylcytosines (oxi-mCs) function as epigenetic marks and likely intermediates in DNA demethylation. Here we present a method based on diglucosylation of 5-hydroxymethylcytosine (5hmC) to simultaneously map 5hmC, 5-formylcytosine, and 5-carboxylcytosine at near-base-pair resolution. We have used the method to map the distribution of oxi-mC across the genome of Coprinopsis cinerea, a basidiomycete that encodes 47 TET/JBP paralogs in a previously unidentified class of DNA transposons. Like 5-methylcytosine residues from which they are derived, oxi-mC modifications are enriched at centromeres, TET/JBP transposons, and multicopy paralogous genes that are not expressed, but rarely mark genes whose expression changes between two developmental stages. Our study provides evidence for the emergence of an epigenetic regulatory system through recruitment of selfish elements in a eukaryotic lineage, and describes a method to map all three different species of oxi-mCs simultaneously.

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Whole-genome analysis of 5-hydroxymethylcytosines and 5-methylcytosines at base resolution in human brain

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Subtraction-free and bisulfite-free specific sequencing of 5-methylcytosine and its oxidized derivatives at base resolution.

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Simultaneous sequencing of oxidized methylcytosines produced by TET/JBP proteins in Coprinopsis cinerea

Project description:This SuperSeries is composed of the SubSeries listed below.

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Subtraction-free and bisulfite-free specific sequencing of 5-methylcytosine and its oxidized derivatives at base resolution

Project description:Although various methods have been developed for sequencing cytosine epigenetic modifications, specific and quantitative sequencing of the two major epigenetic modifications of cytosines, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) at base-resolution is still challenging. Most times it requires subtraction of two methods to obtain both the true 5mC and 5hmC information, which increases noise and requires high sequencing depth. Recently we developed TET assisted pyridine borane sequencing (TAPS) for bisulfite-free direct sequencing of DNA methylation, which provides the sum of 5mC and 5hmC. Here we extend it to two sister methods, TAPSβ and CAPS (Chemical-Assisted Pyridine borane Sequencing), for whole-genome subtraction-free and specific sequencing of 5mC and 5hmC, respectively. We also demonstrated Pyridine borane Sequencing (PS) of whole-genome 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), the further oxidized derivatives of 5mC and 5hmC. This completes the versatile borane reduction chemistry-based methods as a comprehensive suite for direct and quantitative sequencing of all four individual cytosine epigenetic modifications.

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Simultaneous sequencing of oxidized methylcytosines produced by TET/JBP proteins in Coprinopsis cinerea [RNA-seq]

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Individual Brain Charting, a high-resolution fMRI dataset for cognitive mapping.

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Distribution and regulatory roles of oxidized 5-methylcytosines in DNA and RNA of the basidiomycete fungi <i>Laccaria bicolor</i> and <i>Coprinopsis cinerea</i>.

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