DNA Demethylation by TDG

Dalton, Shannon R.; Bellacosa, Alfonso

doi:10.2217/epi.12.36

Cited by 63 publications

(54 citation statements)

References 74 publications

(104 reference statements)

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“…This observation supports the essentiality of TDG for embryonic development and involvement of TDG glycosylase activity in active DNA demethylation. Three possible pathways by which TDG can mediate active DNA demethylation are deamination pathway, hydroxylation-deamination pathway and deamination independent pathway [14]. In all these pathways TDG initiates the BER by excising the modified mC and follow-on BER restore a G•C pair.…”

Section: Editorialmentioning

confidence: 99%

“…and various transcriptional co-activators (CBP/P300, SRC1, NCoR3 etc.) to regulate their functions -playing a role as a transcriptional regulator [14,18,19]. It is well known that cytosine methylation at CpG dinucleotide is an important factor for gene regulation.…”

Section: Editorialmentioning

confidence: 99%

“…TDG also interact with DNA methyltransferase DNMT3a and inhibit the methylation activity of DNMT3a. Thus inhibiting methylation activity of DNMT3a, TDG indirectly regulate CpG methylation and hence gene expression [14,18]. Direct involvement of TDG in gene regulation is through the active DNA demethylation of DNA.…”

Section: Editorialmentioning

confidence: 99%

“…Important role of TDG in DNA repair and active DNA demethylation propose its potential involvement in cancer and tumor genesis. Initial evidence indicates that TDG deficiency or loss of TDG activity increases the chance of tumor and cancer development [14,18]. Extensive research on identifying TDG polymorphism/variant associated with different cancer would advance our understanding of cancer and could provide potential biomarker for specific cancer.…”

Section: Editorialmentioning

confidence: 99%

See 3 more Smart Citations

Versatile Thymine DNA Glycosylase (TDG): Attractive Subject of Future Research and Potential Target for Therapeutics

Maiti¹

2014

J Biomol Res Ther

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Section: Editorialmentioning

confidence: 99%

Section: Editorialmentioning

confidence: 99%

Section: Editorialmentioning

confidence: 99%

Section: Editorialmentioning

confidence: 99%

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Versatile Thymine DNA Glycosylase (TDG): Attractive Subject of Future Research and Potential Target for Therapeutics

Maiti¹

2014

J Biomol Res Ther

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“…This modified base can be either deaminated by AID/Apobec enzymes to give 5-hydroxymethyluracil [Guo et al, 2011] or oxidized into 5-formylcytosine and 5-carboxylcytosine by TET enzymes [Ito et al, 2011]. Both the deamination and the oxidation products are repaired by thymine DNA glycosylase (TDG) enzyme, a glycosylase which is involved in BER [Cortellino et al, 2011;Dalton and Bellacosa, 2012]. A schematic outline of DNA methylation and demethylation mechanisms is reported in Figure 1.…”

mentioning

confidence: 99%

Epigenetics, fragile X syndrome and transcriptional therapy

Tabolacci

Chiurazzi

2013

American J of Med Genetics Pt A

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Epigenetics refers to the study of heritable changes in gene expression that occur without a change in DNA sequence. Epigenetic mechanisms therefore include all transcriptional controls that determine how genes are expressed during development and differentiation, but also in individual cells responding to environmental stimuli. The purpose of this review is to examine the basic principles of epigenetic mechanisms and their contribution to human disorders with a particular focus on fragile X syndrome (FXS), the most common monogenic form of developmental cognitive impairment. FXS represents a prototype of the so-called repeat expansion disorders due to "dynamic" mutations, namely the expansion (known as "full mutation") of a CGG repeat in the 5 0 UTR of the FMR1 gene. This genetic anomaly is accompanied by epigenetic modifications (mainly DNA methylation and histone deacetylation), resulting in the inactivation of the FMR1 gene. The presence of an intact FMR1 coding sequence allowed pharmacological reactivation of gene transcription, particularly through the use of the DNA demethylating agent 5 0 -aza-2 0 -deoxycytydine and/or inhibitors of histone deacetylases. These treatments suggested that DNA methylation is dominant over histone acetylation in silencing the FMR1 gene. The importance of DNA methylation in repressing FMR1 transcription is confirmed by the existence of rare unaffected males carrying unmethylated full mutations. Finally, we address the potential use of epigenetic approaches to targeted treatment of other genetic conditions. Ó 2013 Wiley Periodicals, Inc.Key words: fragile X syndrome; epigenetics; transcriptional therapy INTRODUCTION When in 1942 Conrad H. Waddington coined the term "epigenetics," the exact nature of genes and their role in heredity and in transcriptional regulation was not known; he used it as a conceptual model of how genes might interact with their surroundings to produce a phenotype [Waddington, 1942]. The term is a portmanteau of the words epigenesis (differentiation of cells from their initial totipotent state in embryonic development) and genetics. Only in 2008 at a Cold Spring harbor meeting, consensus was reached on the definition of epigenetic trait, as "stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence" [Berger et al., 2009]. The greek prefix epi-refers to features that are "on top of" genetics, that is, all those stable but reversible changes to DNA, RNA and proteins that regulate gene expression and allow cells with the same DNA to do different things at different times.Broadly speaking, epigenetic mechanisms include all transcriptional controls that regulate gene expression, whether during development and differentiation or in mature cells responding to the environment. Epigenetic changes can be inherited (e.g., imprinting) and be relatively stable (e.g., chromosome X inactivation), but are often rapidly imposed or removed on a given locus according to cell needs. Four major layers of epigenetic controls have ...

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Pyrene‐Based Quantitative Detection of the 5‐Formylcytosine Loci Symmetry in the CpG Duplex Content during TET‐Dependent Demethylation

Chen

Chong

et al. 2014

Angewandte Chemie

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Methylcytosine (5mC) is mostly symmetrically distributed in CpG sites. Ten‐eleven‐translocation (TET) proteins are the key enzymes involved in active DNA demethylation through stepwise oxidation of 5mC. However, oxidation pathways of TET enzymes in the symmetrically methylated CpG context are still elusive. Employing the unique fluorescence properties of pyrene group, we designed and synthesized a sensitive fluorescence‐based probe not only to target 5‐formylcytosine (5fC) sites, but also to distinguish symmetric from asymmetric 5fC sites in the double stranded DNA context during TET‐dependent 5mC oxidation process. Using this novel probe, we revealed dominant levels of symmetric 5fC among total 5fC sites during in vitro TET‐dependent 5mC oxidation and novel mechanistic insights into the TET‐dependent 5mC oxidation in the mCpG context.

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DNA Demethylation by TDG

Cited by 63 publications

References 74 publications

Versatile Thymine DNA Glycosylase (TDG): Attractive Subject of Future Research and Potential Target for Therapeutics

Versatile Thymine DNA Glycosylase (TDG): Attractive Subject of Future Research and Potential Target for Therapeutics

Epigenetics, fragile X syndrome and transcriptional therapy

Pyrene‐Based Quantitative Detection of the 5‐Formylcytosine Loci Symmetry in the CpG Duplex Content during TET‐Dependent Demethylation

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