Evidence map›Paper›PMID 33009383›Full record

ArticleNature communications2020

Functional role of Tet-mediated RNA hydroxymethylcytosine in mouse ES cells and during differentiation.

Jie Lan, Nicholas Rajan, Martin Bizet, Audrey Penning, Nitesh K Singh, Diana Guallar, Emilie Calonne, Andrea Li Greci, Elise Bonvin, Rachel Deplus and 14 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 79 citations in OpenAlex.

  1. Review
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  3. Review
  4. Article
  5. RNA modification systems as therapeutic targets.Nature reviews. Drug discovery · 2026
    Review
  6. Review
  7. Article
  8. Review
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  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. RNA modifications and their role in gene expression.Frontiers in molecular biosciences · 2025
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. TET activity safeguards pluripotency throughout embryonic dormancy.Nature structural & molecular biology · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 7 institutions in 5 countries.

Jie Lan *Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Welbio Investigator, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Nicholas Rajan *Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Welbio Investigator, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Martin BizetLaboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Welbio Investigator, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Audrey PenningLaboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Welbio Investigator, Université Libre de Bruxelles (ULB), Brussels, Belgium.ORCID http://orcid.org/0000-0001-5335-7204
Nitesh K SinghLaboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Welbio Investigator, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Diana GuallarCiMUS, Universidade de Santiago de Compostela-Health Research Institute (IDIS), Santiago de Compostela, Coruña, Spain.ORCID http://orcid.org/0000-0001-5834-7507
Emilie CalonneLaboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Welbio Investigator, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Andrea Li GreciLaboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Welbio Investigator, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Elise BonvinLaboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Welbio Investigator, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Rachel DeplusLaboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Welbio Investigator, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Phillip J HsuDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, and Howard Hughes Medical Institute, University of Chicago, Chicago, IL, 60637, USA.
Sigrid NachtergaeleDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, and Howard Hughes Medical Institute, University of Chicago, Chicago, IL, 60637, USA.
Chengjie MaKey Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, 430072, Wuhan, People's Republic of China.
Renhua SongEpigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown, NSW, 2050, Australia.ORCID http://orcid.org/0000-0002-8228-7281
Alejandro Fuentes-IglesiasCiMUS, Universidade de Santiago de Compostela-Health Research Institute (IDIS), Santiago de Compostela, Coruña, Spain.ORCID http://orcid.org/0000-0002-8634-6701
Bouchra HassabiLaboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Welbio Investigator, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Pascale PutmansLaboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Welbio Investigator, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Frédérique MiesLaboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Welbio Investigator, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Gerben MenschaertDepartment of Mathematical Modeling, Statistics and Bioinformatics, Faculty of Bioscience Engineering, Lab of Bioinformatics and Computational Genomics, Ghent University, Ghent, Belgium.
Justin J L WongEpigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown, NSW, 2050, Australia.ORCID http://orcid.org/0000-0002-7038-5079
Jianlong WangDepartment of Medicine, Columbia Center for Human Development (CCHD), Columbia University Irving Medical Center (CUIMC), New York, NY, 10032, USA.ORCID http://orcid.org/0000-0002-1317-6457
Miguel FidalgoCiMUS, Universidade de Santiago de Compostela-Health Research Institute (IDIS), Santiago de Compostela, Coruña, Spain.ORCID http://orcid.org/0000-0003-1134-2674
Bifeng YuanKey Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, 430072, Wuhan, People's Republic of China.ORCID http://orcid.org/0000-0001-5223-4659
François FuksLaboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Welbio Investigator, Université Libre de Bruxelles (ULB), Brussels, Belgium. ffuks@ulb.ac.be.ORCID http://orcid.org/0000-0003-4637-7287
Université Libre de Bruxelles · BEUniversidade de Santiago de Compostela · ESHoward Hughes Medical Institute · USThe University of Sydney · AUWuhan University · CNColumbia University Irving Medical Center · USGhent University · BE

Funding

MEDICAL SCIENTIST TRAININGT32GM007281 · NIGMS · UNIVERSITY OF CHICAGO · PI CLARK, MARCUS RAMSAY · 1985 to 2022
$32.1M
RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cellsR01HD095938 · NICHD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WANG, JIANLONG · 2018 to 2022
$1.7M
TET2-mediated transcriptional and epigenetic control of normal and malignant hematopoiesisR01HL146664 · NHLBI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI WANG, JIANLONG, XU, MINGJIANG · 2019 to 2022
$1.7M
Transcriptional and Epigenetic Control of Pluripotency and Development by Zfp281R01GM129157 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WANG, JIANLONG · 2018 to 2021
$1.3M
Howard Hughes Medical Institute DRG-2215-15NHLBI NIH HHS R01 HL146664NICHD NIH HHS R01 HD095938NIGMS NIH HHS R01 GM129157NIGMS NIH HHS T32 GM007281
6 · The paper itself

Abstract

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.

Indexed as

Cell Differentiation5-MethylcytosineAnimalsAntibody SpecificityBase SequenceDioxygenasesDNA-Binding ProteinsEmbryoid BodiesMiceModels, BiologicalMouse Embryonic Stem CellsPluripotent Stem CellsProtein BindingProto-Oncogene ProteinsRNARNA, Messenger5-hydroxymethylcytosine5-MethylcytosineDioxygenasesDNA-Binding ProteinsProto-Oncogene ProteinsRNARNA, MessengerTET1 protein, mouseTet2 protein, mouse

Identifiers

PMID33009383
PMCPMC7532169
OpenAlexW3089695391

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.