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Cell Rep
2016 Jan 26;143:493-505. doi: 10.1016/j.celrep.2015.12.044.
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Tet3 Reads 5-Carboxylcytosine through Its CXXC Domain and Is a Potential Guardian against Neurodegeneration.
Jin SG, Zhang ZM, Dunwell TL, Harter MR, Wu X, Johnson J, Li Z, Liu J, Szabó PE, Lu Q, Xu GL, Song J, Pfeifer GP.
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We report that the mammalian 5-methylcytosine (5mC) oxidase Tet3 exists as three major isoforms and characterized the full-length isoform containing an N-terminal CXXC domain (Tet3FL). This CXXC domain binds to unmethylated CpGs, but, unexpectedly, its highest affinity is toward 5-carboxylcytosine (5caC). We determined the crystal structure of the CXXC domain-5caC-DNA complex, revealing the structural basis of the binding specificity of this domain as a reader of CcaCG sequences. Mapping of Tet3FL in neuronal cells shows that Tet3FL is localized precisely at the transcription start sites (TSSs) of genes involved in lysosome function, mRNA processing, and key genes of the base excision repair pathway. Therefore, Tet3FL may function as a regulator of 5caC removal by base excision repair. Active removal of accumulating 5mC from the TSSs of genes coding for lysosomal proteins by Tet3FL in postmitotic neurons of the brain may be important for preventing neurodegenerative diseases.
Blaschke,
Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.
2013, Pubmed
Blaschke,
Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.
2013,
Pubmed Coey,
E2-mediated small ubiquitin-like modifier (SUMO) modification of thymine DNA glycosylase is efficient but not selective for the enzyme-product complex.
2014,
Pubmed Cuervo,
When lysosomes get old.
2000,
Pubmed Dumesic,
Product binding enforces the genomic specificity of a yeast polycomb repressive complex.
2015,
Pubmed Ficz,
Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation.
2011,
Pubmed Gan-Or,
Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease.
2015,
Pubmed Gu,
The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes.
2011,
Pubmed Guan,
The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates DNA repair enzyme TDG glycosylase.
2007,
Pubmed Guo,
Active and passive demethylation of male and female pronuclear DNA in the mammalian zygote.
2014,
Pubmed Hackett,
Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine.
2013,
Pubmed Hahn,
Dynamics of 5-hydroxymethylcytosine and chromatin marks in Mammalian neurogenesis.
2013,
Pubmed Hahn,
5-Hydroxymethylcytosine: a stable or transient DNA modification?
2014,
Pubmed Hansen,
A model for transmission of the H3K27me3 epigenetic mark.
2008,
Pubmed Hardeland,
Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover.
2002,
Pubmed Hashimoto,
Activity and crystal structure of human thymine DNA glycosylase mutant N140A with 5-carboxylcytosine DNA at low pH.
2013,
Pubmed Hashimoto,
Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation.
2012,
Pubmed Hashimoto,
Structure of a Naegleria Tet-like dioxygenase in complex with 5-methylcytosine DNA.
2014,
Pubmed Hassan,
Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes.
2002,
Pubmed He,
Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA.
2011,
Pubmed Hu,
Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation.
2013,
Pubmed Hu,
Tet and TDG mediate DNA demethylation essential for mesenchymal-to-epithelial transition in somatic cell reprogramming.
2014,
Pubmed Huang,
Distinct roles of the methylcytosine oxidases Tet1 and Tet2 in mouse embryonic stem cells.
2014,
Pubmed Iqbal,
Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine.
2011,
Pubmed Ito,
Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification.
2010,
Pubmed Ito,
Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine.
2011,
Pubmed Khare,
5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary.
2012,
Pubmed Klein,
The histone-H3K4-specific demethylase KDM5B binds to its substrate and product through distinct PHD fingers.
2014,
Pubmed Klose,
Genomic DNA methylation: the mark and its mediators.
2006,
Pubmed Ko,
Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX.
2013,
Pubmed Ko,
Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2.
2010,
Pubmed Koh,
DNA methylation and methylcytosine oxidation in cell fate decisions.
2013,
Pubmed Kriaucionis,
The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain.
2009,
Pubmed Lan,
Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression.
2007,
Pubmed Liu,
Quantitative assessment of Tet-induced oxidation products of 5-methylcytosine in cellular and tissue DNA.
2013,
Pubmed Liu,
Intrinsic and extrinsic connections of Tet3 dioxygenase with CXXC zinc finger modules.
2013,
Pubmed Liu,
Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability.
2015,
Pubmed Lu,
Base-resolution maps of 5-formylcytosine and 5-carboxylcytosine reveal genome-wide DNA demethylation dynamics.
2015,
Pubmed Maiti,
Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites.
2011,
Pubmed Margueron,
Role of the polycomb protein EED in the propagation of repressive histone marks.
2009,
Pubmed McLean,
GREAT improves functional interpretation of cis-regulatory regions.
2010,
Pubmed Minor,
Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine.
2013,
Pubmed Münzel,
Quantification of the sixth DNA base hydroxymethylcytosine in the brain.
2010,
Pubmed Palmieri,
Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways.
2011,
Pubmed Parsons,
CHIP-mediated degradation and DNA damage-dependent stabilization regulate base excision repair proteins.
2008,
Pubmed
,
Xenbase Peat,
Genome-wide bisulfite sequencing in zygotes identifies demethylation targets and maps the contribution of TET3 oxidation.
2014,
Pubmed Perera,
TET3 is recruited by REST for context-specific hydroxymethylation and induction of gene expression.
2015,
Pubmed Pfeifer,
5-hydroxymethylcytosine and its potential roles in development and cancer.
2013,
Pubmed Rottach,
The multi-domain protein Np95 connects DNA methylation and histone modification.
2010,
Pubmed Schneider,
Lysosomal function in macromolecular homeostasis and bioenergetics in Parkinson's disease.
2010,
Pubmed Schöndorf,
iPSC-derived neurons from GBA1-associated Parkinson's disease patients show autophagic defects and impaired calcium homeostasis.
2014,
Pubmed Settembre,
TFEB links autophagy to lysosomal biogenesis.
2011,
Pubmed Shacka,
Mouse models of neuronal ceroid lipofuscinoses: useful pre-clinical tools to delineate disease pathophysiology and validate therapeutics.
2012,
Pubmed Shen,
Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes.
2014,
Pubmed Shen,
Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics.
2013,
Pubmed Sidransky,
Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease.
2009,
Pubmed Sobol,
CHIPping away at base excision repair.
2008,
Pubmed Song,
Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation.
2011,
Pubmed Stadler,
DNA-binding factors shape the mouse methylome at distal regulatory regions.
2011,
Pubmed Szulwach,
5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging.
2011,
Pubmed Tahiliani,
Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1.
2009,
Pubmed Torres,
Histone demethylase KDM5A is regulated by its reader domain through a positive-feedback mechanism.
2015,
Pubmed Tsunemoto,
Cis-acting elements (E-box and NBE) in the promoter region of three maternal genes (Histone H1oo, Nucleoplasmin 2, and Zygote Arrest 1) are required for oocyte-specific gene expression in the mouse.
2008,
Pubmed Valinluck,
Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1.
2007,
Pubmed Wen,
Whole-genome analysis of 5-hydroxymethylcytosine and 5-methylcytosine at base resolution in the human brain.
2014,
Pubmed Williams,
TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity.
2011,
Pubmed Wossidlo,
5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming.
2011,
Pubmed Wu,
Reversing DNA methylation: mechanisms, genomics, and biological functions.
2014,
Pubmed Xu,
Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development.
2012,
Pubmed
,
Xenbase Xu,
Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells.
2011,
Pubmed Yamaguchi,
Role of Tet1 in erasure of genomic imprinting.
2013,
Pubmed Yin,
Ascorbic acid enhances Tet-mediated 5-methylcytosine oxidation and promotes DNA demethylation in mammals.
2013,
Pubmed Zhang,
Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA.
2012,
Pubmed Zhang,
Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin.
2008,
Pubmed
