Evidence map›Paper›PMID 34288360›Full record

ArticleEMBO reports2021

Whole-genome analysis of TET dioxygenase function in regulatory T cells.

Xiaojing Yue, Daniela Samaniego-Castruita, Edahí González-Avalos, Xiang Li, Benjamin G Barwick, Anjana Rao

Open access · greenAbstract read
In one paragraph

Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.5field-weighted citation impact, top 9% 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

32 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
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  14. Review
  15. Article
  16. Micronutrient regulation of the DNA methylome.Frontiers in epigenetics and epigenomics · 2024
    Review
  17. Article
  18. TET proteins regulateFrontiers in immunology · 2024
    Article
  19. Article
  20. A Large-Scale Exome-Wide Association Study Identifies Novel Germline Mutations in Lung Cancer.American journal of respiratory and critical care medicine · 2023
    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

6 authors at 2 institutions in 1 country.

Xiaojing YueDivision of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA, USA.ORCID 0000-0002-3385-3857
Daniela Samaniego-CastruitaDivision of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA, USA.ORCID 0000-0001-6082-6603
Edahí González-AvalosDivision of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA, USA.
Xiang LiDivision of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA, USA.
Benjamin G BarwickDepartment of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.ORCID 0000-0001-9810-3566
Anjana RaoDivision of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA, USA.ORCID 0000-0002-1870-1775
La Jolla Institute for Immunology · USEmory University · US

Funding

The TET-DNMT-ASXL1-OGT axis: relevance to clonal hematopoiesis, heterochromatin integrity and cancerR35CA210043 · NCI · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI Anjana Rao · 2016 to 2026
$10.6M
Investigating the role of TET deficiency in promoting T cell expansion and inflammationR01AI128589 · NIAID · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI RAO, ANJANA · 2017 to 2025
$5.3M
Illumina HiSeq 2500 Sequencing SystemS10OD016262 · OD · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI RAO, ANJANA · 2013 to 2013
$600k
FACSAria II Cell SorterS10RR027366 · NCRR · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI CROFT, MICHAEL · 2011 to 2011
$514k
NCI NIH HHS R35 CA210043NCRR NIH HHS S10 RR027366NIAID NIH HHS R01 AI128589NIH HHS S10 OD016262
6 · The paper itself

Abstract

TET methylcytosine dioxygenases are essential for the stability and function of regulatory T cells (Treg cells), which maintain immune homeostasis and self-tolerance and express the lineage-determining transcription factor Foxp3. Here, we use whole-genome analyses to show that the transcriptional program and epigenetic features (DNA modification, chromatin accessibility) of Treg cells are attenuated in the absence of Tet2 and Tet3. Conversely, the addition of the TET activator vitamin C during TGFβ-induced iTreg cell differentiation in vitro potentiates the expression of Treg signature genes and alters the epigenetic landscape to better resemble that of Treg cells generated in vivo. Vitamin C enhances IL-2 responsiveness in iTreg cells by increasing IL2Rα expression, STAT5 phosphorylation, and STAT5 binding, mimicking the IL-2/STAT5 dependence of Treg cells generated in vivo. In summary, TET proteins play essential roles in maintaining Treg molecular features and promoting their dependence on IL-2. TET activity during endogenous Treg development and potentiation of TET activity by vitamin C during iTreg differentiation are necessary to maintain the transcriptional and epigenetic features of Treg cells.

Indexed as

DioxygenasesT-Lymphocytes, RegulatoryCell DifferentiationForkhead Transcription FactorsGene Expression RegulationTransforming Growth Factor betaDioxygenasesForkhead Transcription FactorsTransforming Growth Factor betaepigeneticsIL-2STAT5 signalingTET proteinsTreg cellsvitamin C

Identifiers

PMID34288360
PMCPMC8339674
OpenAlexW3185321524

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.