Abstract
The TET enzymes convert methylcytosine to the newly discovered base hydroxymethylcytosine. While recent reports suggest that TETs may play a role in response to oxidative stress, this role remains uncertain, and results lack in vivo models. Here we show a global decrease of hydroxymethylcytosine in cells treated with buthionine sulfoximine, and in mice depleted for the major antioxidant enzymes GPx1 and 2. Furthermore, genome-wide profiling revealed differentially hydroxymethylated regions in coding genes, and intriguingly in microRNA genes, both involved in response to oxidative stress. These results thus suggest a profound effect of in vivo oxidative stress on the global hydroxymethylome.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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5-Methylcytosine / analogs & derivatives
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5-Methylcytosine / metabolism*
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Animals
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Antimetabolites / pharmacology
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Buthionine Sulfoximine / pharmacology
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Cell Line, Tumor
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Dioxygenases
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Gene Expression Profiling
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Gene Expression Regulation
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Genome*
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Genome-Wide Association Study
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Glutathione / antagonists & inhibitors
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Glutathione / biosynthesis
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Glutathione Peroxidase / deficiency
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Glutathione Peroxidase / genetics
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Glutathione Peroxidase GPX1
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Mice
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Mice, Knockout
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Oxidative Stress
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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Signal Transduction
Substances
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Antimetabolites
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DNA-Binding Proteins
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MicroRNAs
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Proto-Oncogene Proteins
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TET1 protein, mouse
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Buthionine Sulfoximine
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5-Methylcytosine
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Gpx2 protein, mouse
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Glutathione Peroxidase
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Dioxygenases
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Tet2 protein, mouse
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Glutathione
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Glutathione Peroxidase GPX1
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Gpx1 protein, mouse