TET enzymes, TDG and the dynamics of DNA demethylation
Rahul M. Kohli,Yi Zhang +1 more
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TLDR
Methylation, oxidation and repair now offer a model for a complete cycle of dynamic cytosine modification, with mounting evidence for its significance in the biological processes known to involve active demethylation.Abstract:
DNA methylation has a profound impact on genome stability, transcription and development. Although enzymes that catalyse DNA methylation have been well characterized, those that are involved in methyl group removal have remained elusive, until recently. The transformative discovery that ten-eleven translocation (TET) family enzymes can oxidize 5-methylcytosine has greatly advanced our understanding of DNA demethylation. 5-Hydroxymethylcytosine is a key nexus in demethylation that can either be passively depleted through DNA replication or actively reverted to cytosine through iterative oxidation and thymine DNA glycosylase (TDG)-mediated base excision repair. Methylation, oxidation and repair now offer a model for a complete cycle of dynamic cytosine modification, with mounting evidence for its significance in the biological processes known to involve active demethylation.read more
Citations
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Gene expression regulation mediated through reversible m 6 A RNA methylation
TL;DR: This Review focuses on reversible methylation through the most prevalent mammalian mRNA internal modification, N6-methyladenosine (m6A), and indicates dynamic regulatory roles that are analogous to the well-known reversible epigenetic modifications of DNA and histone proteins.
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The CRISPR tool kit for genome editing and beyond.
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TET-mediated active DNA demethylation: mechanism, function and beyond
Xiaoji Wu,Yi Zhang +1 more
TL;DR: Recent advances in biochemical and structural studies have revealed mechanistic insights into how TET and TDG mediate active DNA demethylation and many regulatory mechanisms of this process have been identified.
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Insulator dysfunction and oncogene activation in IDH mutant gliomas
William A. Flavahan,Yotam Drier,Yotam Drier,Yotam Drier,Brian B. Liau,Brian B. Liau,Brian B. Liau,Shawn M. Gillespie,Shawn M. Gillespie,Shawn M. Gillespie,Andrew S. Venteicher,Andrew S. Venteicher,Anat Stemmer-Rachamimov,Mario L. Suvà,Mario L. Suvà,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein +17 more
TL;DR: Human IDH mutant gliomas exhibit hypermethylation at cohesin and CCCTC-binding factor (CTCF)-binding sites, compromising binding of this methylation-sensitive insulator protein, and manifest a CpG island methylator phenotype (G-CIMP), although the functional importance of this altered epigenetic state remains unclear.
Journal ArticleDOI
Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions
TL;DR: The mechanism and function of DNA demethylation in mammalian genomes is discussed, focusing particularly on how developmental modulation of the cytosine-modifying pathway is coupled to active reversal of DNA methylation in diverse biological processes.
References
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Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals
Rudolf Jaenisch,Adrian Bird +1 more
TL;DR: Advances in the understanding of the mechanism and role of DNA methylation in biological processes are reviewed, showing that epigenetic mechanisms seem to allow an organism to respond to the environment through changes in gene expression.
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Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
Mamta Tahiliani,Kian Peng Koh,Yinghua Shen,William A. Pastor,Hozefa S. Bandukwala,Yevgeny Brudno,Suneet Agarwal,Lakshminarayan M. Iyer,David R. Liu,L. Aravind,Anjana Rao +10 more
TL;DR: It is shown here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro.
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Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine
Shinsuke Ito,Li Shen,Qing Dai,Susan C. Wu,Leonard B. Collins,James A. Swenberg,Chuan He,Yi Zhang +7 more
TL;DR: This study raises the possibility that DNA demethylation may occur through Tet-catalyzed oxidation followed by decarboxylation, and identifies two previously unknown cytosine derivatives in genomic DNA as the products of Tet proteins.
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The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain
TL;DR: It is shown that, as well as 5mC in mammalian genomes, there are also significant amounts of 5-hydroxymethylcytosine (5hmC) in DNA of Purkinje neurons, which have large nuclei with apparently very little heterochromatin.
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A decade of exploring the cancer epigenome — biological and translational implications
Stephen B. Baylin,Peter A. Jones +1 more
TL;DR: Next-generation sequencing is providing a window for visualizing the human epigenome and how it is altered in cancer, including linking epigenetic abnormalities to mutations in genes that control DNA methylation, the packaging and the function of DNA in chromatin, and metabolism.