XB-ART-53246
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.
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???displayArticle.grants??? [+]
R01 MH094599 NIMH NIH HHS, NS075393 NINDS NIH HHS , R01 GM064378 NIGMS NIH HHS , CA160965 NCI NIH HHS , GM064378 NIGMS NIH HHS , R01 NS075393 NINDS NIH HHS , R01 CA160965 NCI NIH HHS , MH094599 NIMH NIH HHS
Species referenced: Xenopus
Genes referenced: tet3
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