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The Mammalian de Novo DNA Methyltransferases DNMT3A and DNMT3B Are Also DNA 5-Hydroxymethylcytosine Dehydroxymethylases

Open access
Chen, Chun-Chang, Wang, Keh-Yang, Shen, Che-Kun James·2012·Journal of Biological Chemistry

Abstract

For cytosine (C) demethylation of vertebrate DNA, it is known that the TET proteins could convert 5-methyl C (5-mC) to 5-hydroxymethyl C (5-hmC). However, DNA dehydroxymethylase(s), or enzymes able to directly convert 5-hmC to C, have been elusive. We present in vitro evidence that the mammalian de novo DNA methyltransferases DNMT3A and DNMT3B, but not the maintenance enzyme DNMT1, are also redox-dependent DNA dehydroxymethylases. Significantly, intactness of the C methylation catalytic sites of these de novo enzymes is also required for their 5-hmC dehydroxymethylation activity. That DNMT3A and DNMT3B function bidirectionally both as DNA methyltransferases and as dehydroxymethylases raises intriguing and new questions regarding the structural and functional aspects of these enzymes and their regulatory roles in the dynamic modifications of the vertebrate genomes during development, carcinogenesis, and gene regulation.

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Metadata

Authors
Chen, C.-C., Wang, K.-Y., & Shen, C.-K. J.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2012-09
Volume
287
Issue
40
Pages
33116-33121
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2079161657
Cited by
175
References
5
FWCI
9.53
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: The Mammalian de Novo DNA Methyltransferases DNMT3A and DNMT3B Are Also DNA 5-Hydroxymethylcytosine Dehydroxymethylases. https://app.cochat.ai/papers/10.1074/jbc.c112.406975
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Chen, C.-C., Wang, K.-Y., & Shen, C.-K. J. (2012). The Mammalian de Novo DNA Methyltransferases DNMT3A and DNMT3B Are Also DNA 5-Hydroxymethylcytosine Dehydroxymethylases. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.c112.406975

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