TETonic shift: biological roles of TET proteins in DNA demethylation and transcription
TLDR
The recent discovery that ten-eleven translocation proteins are 5-methylcytosine oxidases has provided several chemically plausible pathways for the reversal of DNA methylation, thus triggering a paradigm shift in understanding of how changes inDNA methylation are coupled to cell differentiation, embryonic development and cancer.Abstract:
In many organisms, the methylation of cytosine in DNA has a key role in silencing 'parasitic' DNA elements, regulating transcription and establishing cellular identity. The recent discovery that ten-eleven translocation (TET) proteins are 5-methylcytosine oxidases has provided several chemically plausible pathways for the reversal of DNA methylation, thus triggering a paradigm shift in our understanding of how changes in DNA methylation are coupled to cell differentiation, embryonic development and cancer.read more
Citations
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Journal ArticleDOI
Function and information content of DNA methylation
TL;DR: These observations indicate that the underlying DNA sequence largely accounts for local patterns of methylation, which is highly informative when studying gene regulation in normal and diseased cells, and it can potentially function as a biomarker.
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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.
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ngs.plot: Quick mining and visualization of next-generation sequencing data by integrating genomic databases
TL;DR: Ngs.plot is a standalone program to visualize enrichment patterns of DNA-interacting proteins at functionally important regions based on next-generation sequencing data and is a useful tool to help fill the gap between massive datasets and genomic information in this era of big sequencing data.
References
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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.
Journal ArticleDOI
Human DNA methylomes at base resolution show widespread epigenomic differences
Ryan Lister,Mattia Pelizzola,Robert H. Dowen,R. David Hawkins,Gary C. Hon,Julian Tonti-Filippini,Joseph R. Nery,Leonard Lee,Zhen Ye,Que Minh Ngo,Lee Edsall,Jessica Antosiewicz-Bourget,Jessica Antosiewicz-Bourget,Ron Stewart,Ron Stewart,Victor Ruotti,Victor Ruotti,A. Harvey Millar,James A. Thomson,Bing Ren,Bing Ren,Joseph R. Ecker +21 more
TL;DR: The first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA-protein interaction for several key regulatory factors were presented in this article.
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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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Epigenetic Reprogramming in Mammalian Development
Wolf Reik,Wendy Dean,Jörn Walter +2 more
TL;DR: What is known about reprogramming in mammals and how it might relate to developmental potency and imprinting are discussed, including whether or not methylation is involved in the control of gene expression during normal development.