Evidence map›Paper›PMID 33352108›Full record

ArticleMolecular cell2021

Functionally distinct roles for TET-oxidized 5-methylcytosine bases in somatic reprogramming to pluripotency.

Blake A Caldwell, Monica Yun Liu, Rexxi D Prasasya, Tong Wang, Jamie E DeNizio, N Adrian Leu, Nana Yaa A Amoh, Christopher Krapp, Yemin Lan, Emily J Shields and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.2field-weighted citation impact, top 11% 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

33 citing papers in PubMed, 48 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. DNA Methylation Dynamics inBiomolecules · 2026
    Article
  5. Article
  6. Review
  7. Uncovering ParB-dependent and -independent subclasses of T-dioxygenases from bacteriophage.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Cell identity and 5-hydroxymethylcytosine.Epigenetics & chromatin · 2025
    Review
  12. Cell reprogramming: methods, mechanisms and applications.Cell regeneration (London, England) · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. DNA Methylation Machinery in Gastropod Mollusks.Life (Basel, Switzerland) · 2024
    Review
  19. Article
  20. 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

14 authors at 1 institution in 1 country.

Blake A CaldwellDepartment of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Monica Yun LiuDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rexxi D PrasasyaDepartment of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Tong WangDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jamie E DeNizioDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
N Adrian LeuDepartment of Biomedical Sciences, School of Veterinary Medicine, Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Nana Yaa A AmohDepartment of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Christopher KrappDepartment of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yemin LanPenn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Emily J ShieldsDepartment of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Roberto BonasioDepartment of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Christopher J LengnerDepartment of Biomedical Sciences, School of Veterinary Medicine, Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rahul M KohliDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: rkohli@pennmedicine.upenn.edu.
Marisa S BartolomeiDepartment of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: bartolom@pennmedicine.upenn.edu.
University of Pennsylvania · US

Funding

PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM008216 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, DOUGLAS J · 1987 to 2023
$8.3M
VANADIUM INTERACTION STUDIES IN RELATION TO THE INHIBITION OF NA+-K+-ATPASES06GM008216 · NIGMS · UNIVERSITY OF PUERTO RICO AT HUMACAO · PI ALEGRIA, ANTONIO E · 1989 to 2010
$8.0M
SEQUENCES CONTROLLING H19 GENE IMPRINTINGR01GM051279 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BARTOLOMEI, MARISA S. · 1994 to 2024
$5.1M
Ultra low-input epigenetic sequencing with combined enzymatic and long-read technologiesR01HG010646 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI Gang Fang, Rahul Manu Kohli · 2019 to 2026
$3.9M
Sequences controlling H19 Gene ImprintingR37GM051279 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BARTOLOMEI, MARISA S. · 2011 to 2020
$3.9M
Function and RNA-mediated regulation of SCMH1 in Polycomb repressionR01GM127408 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BONASIO, ROBERTO · 2018 to 2021
$1.3M
The mechanism and modulation of 5-methylcytosine oxidation by TET family enzymesR01GM118501 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI KOHLI, RAHUL MANU · 2017 to 2020
$1.2M
Investigation of the role of TET proteins in epigenetic reprogramming and establishment of germline imprintingF32HD101230 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI PRASASYA, REXXI DIPTYA · 2020 to 2022
$208k
Investigating the roles of active DNA demethylation pathways in epigenetic reprogrammingF31HD098764 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI CALDWELL, BLAKE ALEXANDER · 2019 to 2021
$93k
NHGRI NIH HHS R01 HG010646NICHD NIH HHS F31 HD098764NICHD NIH HHS F32 HD101230NIGMS NIH HHS R01 GM051279NIGMS NIH HHS R01 GM118501NIGMS NIH HHS R01 GM127408NIGMS NIH HHS R37 GM051279NIGMS NIH HHS S06 GM008216NIGMS NIH HHS T32 GM008216
6 · The paper itself

Abstract

Active DNA demethylation via ten-eleven translocation (TET) family enzymes is essential for epigenetic reprogramming in cell state transitions. TET enzymes catalyze up to three successive oxidations of 5-methylcytosine (5mC), generating 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), or 5-carboxycytosine (5caC). Although these bases are known to contribute to distinct demethylation pathways, the lack of tools to uncouple these sequential oxidative events has constrained our mechanistic understanding of the role of TETs in chromatin reprogramming. Here, we describe the first application of biochemically engineered TET mutants that unlink 5mC oxidation steps, examining their effects on somatic cell reprogramming. We show that only TET enzymes proficient for oxidation to 5fC/5caC can rescue the reprogramming potential of Tet2-deficient mouse embryonic fibroblasts. This effect correlated with rapid DNA demethylation at reprogramming enhancers and increased chromatin accessibility later in reprogramming. These experiments demonstrate that DNA demethylation through 5fC/5caC has roles distinct from 5hmC in somatic reprogramming to pluripotency.

Indexed as

Cellular ReprogrammingEnhancer Elements, GeneticEpigenesis, Genetic5-MethylcytosineAnimalsDioxygenasesDNA-Binding ProteinsEmbryo, MammalianFibroblastsHEK293 CellsHumansMiceMice, KnockoutMutationNIH 3T3 CellsProto-Oncogene Proteins5-MethylcytosineDioxygenasesDNA-Binding ProteinsProto-Oncogene ProteinsTet2 protein, mouse5caC5-carboxycytosine5fC5-formylcytosine5hmC5-hydroxymethylcytosinebACE-seqDNA demethylationepigeneticsinduced pluripotent stem cellsiPSCsreprogrammingten-eleven translocationTET

Identifiers

PMID33352108
PMCPMC7897302
OpenAlexW3115449903

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.