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TET-mediated DNA oxidation sustains intestinal homeostasis and protects from stressors.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE241808 | GEO | 2023/09/04

REPOSITORIES: GEO

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Genome-wide analysis reveals TET- and TDG-mediated 5-methylcytosine oxidation dynamics

Project description:Ten-eleven translocation (Tet) family of DNA dioxygenases converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5- carboxylcytosine (5caC) through iterative oxidation reactions. While 5mC and 5hmC are relatively abundant, 5fC and 5caC are at very low levels in the mammalian genome. Thymine DNA glycosylase (TDG) and base excision repair (BER) pathways can actively remove 5fC/5caC to regenerate unmethylated cytosine, but it is unclear to what extent and at which part of the genome such active demethylation processes take place. Here, we have performed high-throughput sequencing analysis of 5mC/5hmC/5fC/5caC- enriched DNA using modification-specific antibodies and generated genome-wide distribution maps of these cytosine modifications in wild-type and Tdg-deficient mouse embryonic stem cells (ESCs). We observe that the steady state 5fC and 5caC are preferentially detected at repetitive sequences in wild-type mouse ESCs. Depletion of TDG causes marked accumulation of 5fC and 5caC at a large number of distal gene regulatory elements and transcriptionally repressed/poised gene promoters, suggesting that Tet/TDG-dependent dynamic cycling of 5mC oxidation states may be involved in regulating the function of these regions. Thus, comprehensive mapping of 5mC oxidation and BER pathway activity in the mammalian genome provides a promising approach for better understanding of biological roles of DNA methylation and demethylation dynamics in development and diseases.

2013-04-18 | GSE42250 | GEO

TET-mediated 5-methylcytosine oxidation in tRNA promotes translation.

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Genome-wide analysis reveals TET- and TDG-mediated 5-methylcytosine oxidation dynamics [MeDIP-Seq]

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Ascorbic acid enhances Tet-mediated 5-methylcytosine oxidation and promotes DNA demethylation in mammals.

Project description:DNA demethylation occurs in multiple cellular processes but its regulation is poorly understood. Here we report that a vital nutrient factor ascorbic acid (AA), or vitamin C (Vc), induces DNA demethylation in mammalian cells. The levels of active 5mC oxidation products, 5-formylcytosine and 5-carboxylcytosine, increase by more than one magnitude of order in mouse ES cells when cultured in the presence of AA. In cells deleted of Tet1 and Tet2 dioxygenase genes, AA does not facilitate 5mC oxidation. The AA effect is however restored when Tet2 was re-expressed in the mutant cells. The enhancing effect of AA on 5mC oxidation and DNA demethylation was also observed in a mouse model deficient in AA synthesis. Our results thus reveal a role of AA in the regulation of DNA modification, which might mediate a plethora of functions of AA.

2015-01-01 | GSE43262 | GEO

Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation.

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Creatine maintains intestinal homeostasis and protects against colitis.

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Arsenite Targets the Zinc Finger Domains of Tet Proteins and Inhibits Tet-Mediated Oxidation of 5-Methylcytosine.

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TET-mediated oxidation of methylcytosine causes TDG or NEIL glycosylase dependent gene reactivation.

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