Transcriptome-wide distribution and function of RNA hydroxymethylcytosine
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE66090 | GEO | 2016/01/15
SECONDARY ACCESSION(S): PRJNA275858
REPOSITORIES: GEO
Similar Datasets
Project description:Tet-enzyme-mediated 5-hydroxymethylation of cytosine in DNA plays a crucial role in mouse embryonic stem cells (ESCs). In RNA also, 5-hydroxymethylcytosine (5hmC) has recently been evidenced, but its physiological roles are still largely unknown. Here we show the contribution and function of this mark in mouse ESCs and differentiating embryoid bodies. Transcriptome-wide mapping in ESCs revealed hundreds of messenger RNAs marked by 5hmC at sites characterized by a defined unique consensus sequence and particular features. During differentiation a large number of transcripts, including many encoding key pluripotency-related factors (such as Eed and Jarid2), showed decreased cytosine hydroxymethylation. Using Tet-knockout ESCs, we found Tet enzymes to be partly responsible for deposition of 5hmC in mRNA. A transcriptome-wide search further revealed mRNA targets to which Tet1 and Tet2 bind, at sites showing a topology similar to that of 5hmC sites. Tet-mediated RNA hydroxymethylation was found to reduce the stability of crucial pluripotency-promoting transcripts. We propose that RNA cytosine 5-hydroxymethylation by Tets is a mark of transcriptome flexibility, inextricably linked to the balance between pluripotency and lineage commitment.
2020-07-16 | GSE131899 | GEO
Project description:Tet-enzyme-mediated 5-hydroxymethylation of cytosine in DNA plays a crucial role in mouse embryonic stem cells (ESCs). In RNA also, 5-hydroxymethylcytosine (5hmC) has recently been evidenced, but its physiological roles are still largely unknown. Here we show the contribution and function of this mark in mouse ESCs and differentiating embryoid bodies. Transcriptome-wide mapping in ESCs revealed hundreds of messenger RNAs marked by 5hmC at sites characterized by a defined unique consensus sequence and particular features. During differentiation a large number of transcripts, including many encoding key pluripotency-related factors (such as Eed and Jarid2), showed decreased cytosine hydroxymethylation. Using Tet-knockout ESCs, we found Tet enzymes to be partly responsible for deposition of 5hmC in mRNA. A transcriptome-wide search further revealed mRNA targets to which Tet1 and Tet2 bind, at sites showing a topology similar to that of 5hmC sites. Tet-mediated RNA hydroxymethylation was found to reduce the stability of crucial pluripotency-promoting transcripts. We propose that RNA cytosine 5-hydroxymethylation by Tets is a mark of transcriptome flexibility, inextricably linked to the balance between pluripotency and lineage commitment.
2020-07-16 | GSE131898 | GEO
Project description:Tet-enzyme-mediated 5-hydroxymethylation of cytosine in DNA plays a crucial role in mouse embryonic stem cells (ESCs). In RNA also, 5-hydroxymethylcytosine (5hmC) has recently been evidenced, but its physiological roles are still largely unknown. Here we show the contribution and function of this mark in mouse ESCs and differentiating embryoid bodies. Transcriptome-wide mapping in ESCs revealed hundreds of messenger RNAs marked by 5hmC at sites characterized by a defined unique consensus sequence and particular features. During differentiation a large number of transcripts, including many encoding key pluripotency-related factors (such as Eed and Jarid2), showed decreased cytosine hydroxymethylation. Using Tet-knockout ESCs, we found Tet enzymes to be partly responsible for deposition of 5hmC in mRNA. A transcriptome-wide search further revealed mRNA targets to which Tet1 and Tet2 bind, at sites showing a topology similar to that of 5hmC sites. Tet-mediated RNA hydroxymethylation was found to reduce the stability of crucial pluripotency-promoting transcripts. We propose that RNA cytosine 5-hydroxymethylation by Tets is a mark of transcriptome flexibility, inextricably linked to the balance between pluripotency and lineage commitment.
2020-07-16 | GSE131900 | GEO
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.
2024-04-02 | GSE250415 | GEO
Project description:TET proteins convert 5-methylcytosine to 5-hydroxymethylcytosine, an emerging dynamic epigenetic state of DNA that can influence transcription. While Tet proteins have been associated to epigenetic repression or activation complexes, our understanding of the molecular mechanisms involved in Tet-mediated regulation of gene transcription remains limited. Here, we showed that Tet directly interact with lymphoid-specific helicase (Lsh), a chromatin remodelling factor belonging to the ISWI family. This specific interaction seems to regulate Tet enzymatic activity since Lsh knock-out leads to a substantial reduction of 5-hydroxymethylation global level in mouse embryonic fibroblasts (MEFs) and in embryonic stem cells (ES). Whole genome sequencing of 5hmC in wild-type versus Lsh knock-out MEFs and ESCs showed that in absence of Lsh some regions of the genome gain while others loose 5hmC marks, with a weak correlation to gene expression changes . We further demonstrated that 5hmC modifications upon Lsh loss are not a direct consequence of 5mC decrease as DhMR (differentially hydroxymethylated regions) did not overlap with DMR (differentially methylated regions) underlying that these modifications occurred at different genomic loci. Altogether, our results suggest that DNA 5-hydroxymethylation and nucleosome folding are linked phenomena, highlighting novel means by which Tet proteins may influence gene regulation.
2021-01-31 | GSE110129 | GEO
Project description:The TET-family enzymes (TETs) convert methylcytosine to hydroxymethylcytosine, a lately discovered epigenetic modification that can modulate transcription. While recent reports suggest that TETs may play a role in response to oxidative stress, this role remains uncertain. Here we show that Tet1 is sensitive to peroxide and report a global decrease in hydroxymethylcytosine in cells treated with BSO and in the intestinal epithelium of mice lacking the major antioxidant enzymes glutathione peroxidases 1 and 2. Furthermore, genome-wide profiling revealed differentially hydroxymethylated regions in genes involved in responses to oxidative stress. Intriguingly, a considerable proportion of these regions lie in genes encoding microRNAs predicted to target transcripts involved in oxidative stress response. This work thus demonstrates a profound effect of oxidative stress on the hydroxymethylome and opens exciting new avenues of research by highlighting a set of microRNAs that may participate in the prevention or etiology of oxidative-stress-related diseases. Examination of DNA hydroxymethylation landscape in SY5Y cell lines and in intestinal epithelium of mice.
2016-01-14 | E-GEOD-59718 | biostudies-arrayexpress
Project description:Modifications of mRNA, especially methylation of adenosine, have recently drawn much attention. The much rarer modification, 5-hydroxymethylation of cytosine (5hmC), is not well understood and is the subject of this study. Vertebrate Tet proteins are 5-methylcytosine (5mC) hydroxylases enzymes catalyzing the transition of 5mC to 5hmC in DNA and have recently been shown to have the same function in messenger RNAs in both vertebrates and in Drosophila. The Tet gene is essential in Drosophila because Tet knock-out animals do not reach adulthood. We describe the identification of Tet-target genes in the embryo and larval brain by determining Tet DNA-binding sites throughout the genome and by mapping the Tet-dependent 5hmrC modifications transcriptome-wide. 5hmrC-modified sites can be found along the entire transcript and are preferentially located at the promoter where they overlap with histone H3K4me3 peaks. The identified mRNAs are frequently involved in neuron and axon development and Tet knock-out led to a reduction of 5hmrC marks on specific mRNAs. Among the Tet-target genes were the robo2 receptor and its slit ligand that function in axon guidance in Drosophila and in vertebrates. Tet knock-out embryos show overlapping phenotypes with robo2 and are sensitized to reduced levels of slit. Both Robo2 and Slit protein levels were markedly reduced in Tet KO larval brains. Our results establish a role for Tet-dependent 5hmrC in facilitating the translation of modified mRNAs, primarily in developing nerve cells.
2024-02-23 | GSE225970 | GEO
Project description:Modifications of mRNA, especially methylation of adenosine, have recently drawn much attention. The much rarer modification, 5-hydroxymethylation of cytosine (5hmC), is not well understood and is the subject of this study. Vertebrate Tet proteins are 5-methylcytosine (5mC) hydroxylases enzymes catalyzing the transition of 5mC to 5hmC in DNA and have recently been shown to have the same function in messenger RNAs in both vertebrates and in Drosophila. The Tet gene is essential in Drosophila because Tet knock-out animals do not reach adulthood. We describe the identification of Tet-target genes in the embryo and larval brain by determining Tet DNA-binding sites throughout the genome and by mapping the Tet-dependent 5hmrC modifications transcriptome-wide. 5hmrC-modified sites can be found along the entire transcript and are preferentially located at the promoter where they overlap with histone H3K4me3 peaks. The identified mRNAs are frequently involved in neuron and axon development and Tet knock-out led to a reduction of 5hmrC marks on specific mRNAs. Among the Tet-target genes were the robo2 receptor and its slit ligand that function in axon guidance in Drosophila and in vertebrates. Tet knock-out embryos show overlapping phenotypes with robo2 and are sensitized to reduced levels of slit. Both Robo2 and Slit protein levels were markedly reduced in Tet KO larval brains. Our results establish a role for Tet-dependent 5hmrC in facilitating the translation of modified mRNAs, primarily in developing nerve cells.
2024-02-23 | GSE225969 | GEO
Project description:Modifications of mRNA, especially methylation of adenosine, have recently drawn much attention. The much rarer modification, 5-hydroxymethylation of cytosine (5hmC), is not well understood and is the subject of this study. Vertebrate Tet proteins are 5-methylcytosine (5mC) hydroxylases enzymes catalyzing the transition of 5mC to 5hmC in DNA and have recently been shown to have the same function in messenger RNAs in both vertebrates and in Drosophila. The Tet gene is essential in Drosophila because Tet knock-out animals do not reach adulthood. We describe the identification of Tet-target genes in the embryo and larval brain by determining Tet DNA-binding sites throughout the genome and by mapping the Tet-dependent 5hmrC modifications transcriptome-wide. 5hmrC-modified sites can be found along the entire transcript and are preferentially located at the promoter where they overlap with histone H3K4me3 peaks. The identified mRNAs are frequently involved in neuron and axon development and Tet knock-out led to a reduction of 5hmrC marks on specific mRNAs. Among the Tet-target genes were the robo2 receptor and its slit ligand that function in axon guidance in Drosophila and in vertebrates. Tet knock-out embryos show overlapping phenotypes with robo2 and are sensitized to reduced levels of slit. Both Robo2 and Slit protein levels were markedly reduced in Tet KO larval brains. Our results establish a role for Tet-dependent 5hmrC in facilitating the translation of modified mRNAs, primarily in developing nerve cells.
2024-02-23 | GSE225979 | GEO
Project description:In mammals, cytosine methylation (5mC) is widely distributed throughout the genome but is notably depleted from active promoters and enhancers. While the role of DNA methylation in promoter silencing has been well documented, the function of this epigenetic mark at enhancers remains unclear. Recent experiments have demonstrated that enhancers are enriched for 5-hydroxymethylcytosine (5hmC), an oxidization product of the Tet family of 5mC dioxygenases and an intermediate of DNA demethylation. These results support the involvement of Tet proteins in the regulation of dynamic DNA methylation at enhancers. By mapping DNA methylation and hydroxymethylation at base resolution, we find that deletion of Tet2 causes extensive loss of 5hmC at enhancers, accompanied by enhancer hypermethylation, reduction of enhancer activity, and delayed gene induction in the early steps of differentiation. Our results reveal that DNA demethylation modulates enhancer activity, and its disruption influences the timing of transcriptome reprogramming during cellular differentiation. We performed traditional bisulfite sequencing, TAB-Seq, RNA-Seq, and ChIP-Seq for 6 histone modifications in two biological replicates of wild-type, Tet1-/-, and Tet2-/- mouse ES cells. We also performed RNA-Seq analysis during a timecourse of differentiation to neural progenitor cells.
2014-09-25 | E-GEOD-48519 | biostudies-arrayexpress