Abstract
Although DNA methylation patterns in somatic cells are thought to be relatively stable, they undergo dramatic changes during embryonic development, gametogenesis, and during malignant transformation. The enzymology of DNA methyltransferases is well understood, but the mechanism that removes methylated cytosines from DNA (active DNA demethylation) has remained enigmatic. Recently, a role of the growth arrest and DNA damage inducible protein GADD45A in DNA demethylation has been reported [1]. We have investigated the function of GADD45A in DNA demethylation in more detail using gene reactivation and DNA methylation assays. Contrary to the previous report, we were unable to substantiate a functional role of GADD45A in DNA demethylation. The mechanism of active DNA demethylation in mammalian cells remains unknown.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Base Sequence
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Cell Cycle Proteins / genetics*
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Cell Cycle Proteins / metabolism*
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DNA Methylation*
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DNA Primers / genetics
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Embryonic Development / genetics
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Embryonic Development / physiology
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Endonucleases / genetics
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Endonucleases / metabolism
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Female
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Gene Expression Profiling
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Gene Expression Regulation, Developmental
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Genes, Reporter
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Green Fluorescent Proteins / genetics
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Humans
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Mice
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NIH 3T3 Cells
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism*
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Oocytes / metabolism
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Plasmids / genetics
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Pregnancy
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Recombinant Proteins / genetics
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transfection
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Zygote / metabolism
Substances
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Cell Cycle Proteins
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DNA Primers
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DNA excision repair protein ERCC-5
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DNA-Binding Proteins
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GADD45A protein, human
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Gadd45a protein, mouse
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Nuclear Proteins
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Recombinant Proteins
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Transcription Factors
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enhanced green fluorescent protein
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Green Fluorescent Proteins
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Endonucleases