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Keywords {🔍}

tet, hmc, pubmed, escs, data, transcripts, rna, fig, google, scholar, cas, supplementary, cell, central, mrna, cells, hydroxymethylation, tko, differentiation, dna, mouse, peaks, nature, tetmediated, stem, performed, identified, showing, experiments, targets, mrnas, hmcmodified, stability, analysis, embryonic, level, expression, hmeripseq, role, gene, transcript, hydroxymethylcytosine, found, reads, pluripotencyrelated, pluripotency, esc, ebs, unmodified, ads,

Topics {✒️}

crispr genome-editing tool nature portfolio privacy policy horseradish-peroxidase-conjugated anti-mouse advertising io/picard/ hrp-linked anti-rat igg fnrs-welbio-cr-2019a-04r lc–esi-ms/ms analysis social media middle parts tools reprints crispr-cas9-targeted genomic regions research design santiago de compostela protein o-glycosylation marks44 performed paired-end rna-seq macs2 “-call-summits” option �–call-summits” macs2 option source data file hmerip-seq data sets molecular biology high-throughput sequencing data rip-seq data supporting flag + ha + twin-strep macs2 peak-calling tool63 thermofisher scientific tet-mediated rna hydroxymethylation α-kg-dependent dioxygenases fine-tuning gene expression fnrs-welbio-cr-2017a-04 nature 500 nature 468 nature 477 nature 466 nature 473 nature 554 nature 493 nature key pluripotency-related mrnas research tet-mediated dna hydroxymethylation c-terminal catalytic domain38 encode pluripotency-related factors key pluripotency-related transcripts fast gapped-read alignment comparing tet1/2-bound 5hmc-modified diverse chromatin-related machineries crispr-cas9 nuclease system56

Questions {❓}

• What is the contribution of Tet proteins to mRNA hydroxymethylation in ESCs?
• What might be the function of Tet1/2-mediated mRNA hydroxymethylation in ESCs?

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         headline:Functional role of Tet-mediated RNA hydroxymethylcytosine in mouse ES cells and during differentiation
         description:Tet-enzyme-mediated 5-hydroxymethylation of cytosines 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 reveals 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), show decreased cytosine hydroxymethylation. Using Tet-knockout ESCs, we find Tet enzymes to be partly responsible for deposition of 5hmC in mRNA. A transcriptome-wide search further reveals mRNA targets to which Tet1 and Tet2 bind, at sites showing a topology similar to that of 5hmC sites. Tet-mediated RNA hydroxymethylation is 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. TET mediated RNA-hydroxymethylation (5hmC) has been detected in mammals, but its physiological role remains unclear. Here the authors map 5hmC during embryonic stem cell (ESC) differentiation and find that Tet-mediated RNA hydroxymethylation reduces the stability of crucial pluripotency related transcripts.
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      headline:Functional role of Tet-mediated RNA hydroxymethylcytosine in mouse ES cells and during differentiation
      description:Tet-enzyme-mediated 5-hydroxymethylation of cytosines 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 reveals 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), show decreased cytosine hydroxymethylation. Using Tet-knockout ESCs, we find Tet enzymes to be partly responsible for deposition of 5hmC in mRNA. A transcriptome-wide search further reveals mRNA targets to which Tet1 and Tet2 bind, at sites showing a topology similar to that of 5hmC sites. Tet-mediated RNA hydroxymethylation is 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. TET mediated RNA-hydroxymethylation (5hmC) has been detected in mammals, but its physiological role remains unclear. Here the authors map 5hmC during embryonic stem cell (ESC) differentiation and find that Tet-mediated RNA hydroxymethylation reduces the stability of crucial pluripotency related transcripts.
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         Embryonic stem cells
         Molecular biology
         RNA
         Science
         Humanities and Social Sciences
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