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Ten-eleven translocation (Tet) methylcytosine dioxygenases dependent viral DNA demethylation mediates in vivo hepatitis B virus (HBV) biosynthesis

ABSTRACT: Liver-specific ten-eleven translocation methylcytosine dioxygenases 2 and 3 (Tet2 plus Tet3)-deficient hepatitis B virus (HBV) transgenic mice fail to support viral biosynthesis. The levels of viral transcription and replication intermediates are dramatically reduced. Hepatitis B core antigen (HBcAg) is only observed in a very limited number of pericentral hepatocytes in a pattern that is similar to glutamate-ammonia ligase (Glul), a -catenin target gene. HBV transcript abundance in Tet-deficient mice resembles that observed in wild-type neonatal mice. Furthermore, the RNA levels of several -catenin target genes including Glul, Lhpp, Notun, Oat, Slc1a2 and Tbx3, in Tet-deficient mice was also similar to that observed in wild-type neonatal mice. As HBV transcription is regulated by -catenin, these finding support the suggestion that neonatal Tet-deficiency might limit -catenin target gene expression, limiting viral biosynthesis. Additionally, HBV transgene DNA displays increased 5-methylcytosine (5mC) frequency at CpG sequences consistent with neonatal Tet-deficiency being responsible for decreased developmental viral DNA demethylation mediated by 5mC oxidation to 5-hydroxymethylcytosine (5hmC), a process that might be responsible for the reduction in cellular -catenin target gene expression and viral transcription and replication.

ORGANISM(S): Hepatitis B virus

PROVIDER: GSE242448 | GEO | 2023/11/29

REPOSITORIES: GEO

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Relative DNA methylation and demethylation efficiencies during postnatal liver development regulate hepatitis B virus biosynthesis

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2020-12-10 | GSE157451 | GEO

Generation and molecular characterisation of transient tet1/2/3 zebrafish knockouts

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Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects [Joint-snhmC-seq: snhmCseq2.split]

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Tet2-mediated DNA demethylation controls T cell cytokine expression [seq]

Project description:The conversion of 5-methylcytosine (5mC) into 5-Hydroxymethylcytosine (5hmC) by ten-eleven translocation (Tet) family has recently been identified as a key process for active DNA demethylation, whose effects in the immune response is currently unknown. Examination of both 5mC and 5hmC modifications in 5 Th cell types. CD2(Cre)Tet2(f/f) mice (previously described in Moran-Crusio et al.,2011) and wild-type littermates on the mixed background were used in experiments.

2015-04-12 | E-GEOD-49139 | biostudies-arrayexpress

Distinct and stage-specific contributions of TET1 and TET2 to stepwise cytosine oxidation in the transition from naive to primed pluripotency

Project description:Cytosine DNA bases can be methylated by DNA methyltransferases and subsequently oxidized by TET proteins. The resulting 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) are considered demethylation intermediates as well as stable epigenetic marks. To dissect the contribution of these cytosine modifying enzymes, we generated combinations of Tet knockout (KO) embryonic stem cells (ESCs) and systematically measured protein and DNA modification levels at the transition from naive to primed pluripotency. Whereas the increase of genomic 5-methylcytosine (5mC) levels during exit from pluripotency correlated with an upregulation of the de novo DNA methyltransferases DNMT3A and DNMT3B, the subsequent oxidation steps turned out to be far more complex. The strong increase of oxidized cytosine bases (5hmC, 5fC, and 5caC) was accompanied by a drop in TET2 levels, yet the analysis of KO cells suggested that TET2 is responsible for most 5fC formation. The comparison of modified cytosine and enzyme levels in Tet KO cells revealed distinct and differentiation-dependent contributions of TET1 and TET2 to 5hmC and 5fC formation arguing against a processive mechanism of 5mC oxidation. The apparent independent steps of 5hmC and 5fC formation suggest yet to be identified mechanisms regulating TET activity and may constitute another layer of epigenetic regulation.

2020-07-24 | PXD019514 | Pride

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Project description:Enzymes of the Ten Eleven Translocation (TET) family play a key role in the regulation of gene expression in many species by oxidizing 5-methylcytosine (5mC), a prominent epigenetic mark, into 5-hydroxymethylcytosine (5hmC). Yet, TET proteins also have non-canonical modes of action beyond 5mC oxidation, notably in Drosophila, whose genomes is devoid of 5mC. Here, we used a combination of NGS analyses to studied the funciton and mode of action of Tet in the central nervous system of Drosophila larvae.

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Rest recruits neuronal Tet3 to induce chromatin remodeling and gene expression

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2015-04-02 | PXD001857 | Pride

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