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Epigenetics

Epigenetic locking of Foxp3 in Tregs

Floess S, Freyer J, Siewert C, et al. · PLoS biology · 2007

Open access · cc by · source: Europe PMC

Stable regulatory T cells fully demethylate a conserved foxp3 region; TGF-β–induced Tregs do not.

Study at a glance

Design
Animal / in-vitro — Bisulphite sequencing and ChIP of foxp3/TSDR in natural vs TGF-β–induced regulatory T cells
N
Epigenetic comparison of Treg populations — no single primary analytic N in stored text
Population
Natural and induced Foxp3+ regulatory T cells (and comparator thymocytes)
Outcome
Demethylation of foxp3 regulatory regions predicting Treg stability

Structured fields used in claim comparison tables when every cited study has a complete layer.

Key findings

TSDR-like element is demethylated in stable Tregs; weak demethylation predicts unstable induced Foxp3.

Methodology

Bisulphite sequencing and ChIP compared natural Tregs, thymocytes, and TGF-β–induced Foxp3+ cells.

Limitations

Mostly mouse data; human translation needs care.

How this study connects

Role on claims

Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.

  • SupportsEpigeneticsconcept

    Multiple empirical papers in this library examine epigenetics with mechanistic biological findings.

    Evidence for the claim as stated.

  • SupportsEpigeneticsconcept

    TSDR-like element is demethylated in stable Tregs; weak demethylation predicts unstable induced Foxp3.

    Evidence for the claim as stated.

  • SupportsEpigeneticsconcept

    Systems and scales differ across epigenetics studies (species, tissues, methods), so mechanisms should not be over-generalised.

    Evidence for the claim as stated.

  • SupportsFlow Cytometrymethod

    Foxp3 locus work compared natural Tregs, thymocytes and TGF-β–induced Foxp3+ cells by bisulphite sequencing and ChIP: a TSDR-like element is demethylated in stable Tregs, and weak demethylation predicts unstable induced Foxp3. Flow is typically how those Foxp3+ populations are defined, but the headline methods are epigenetic, and the data are mostly mouse.

    Evidence for the claim as stated.

  • SupportsFlow Cytometrymethod

    Foxp3+ gating is a means to an epigenetic comparison (TSDR demethylation versus unstable induced Foxp3), whereas spike and Naegleria papers are trafficking genetics and a genome assembly. Treating every hit as a flow-cytometry methods paper hides those mismatches.

    Evidence for the claim as stated.

  • Two papers are weak luciferase examples. Foxp3 stability was scored by bisulphite sequencing and ChIP: a TSDR-like element is demethylated in stable Tregs, and weak demethylation predicts unstable TGF-β–induced Foxp3 (mostly mouse). ZFP36 family members are growth-factor immediate-early genes that bind metabolic mRNAs, promote Eno2 decay, raise ENO2/PEP when lost, and affect neonatal retinal angiogenesis — eCLIP and metabolomics, not a promoter-luciferase paper.

    Evidence for the claim as stated.

  • MC4R shows that a cAMP/reporter signal can look normal while trafficking is impaired, so luciferase-like pathway readouts disagree with surface-expression assays. Foxp3 and ZFP36 papers barely use luciferase at all: DNA methylation/ChIP versus mRNA decay and metabolomics.

    Evidence for the claim as stated.

  • SupportsChIP-seqmethod

    Foxp3 locus ChIP plus bisulphite sequencing compared natural Tregs, thymocytes and TGF-β–induced Foxp3+ cells: a TSDR-like element is demethylated in stable Tregs, and weak demethylation predicts unstable induced Foxp3. This 2007 design is locus-specific ChIP and methylation, mostly in mouse, not a genome-wide ChIP-seq of histone marks.

    Evidence for the claim as stated.

  • SupportsChIP-seqmethod

    Only the rice histone-acylation paper is clearly genome-wide ChIP-seq of chromatin marks (Kbu/Kcr versus H3K9ac under stress). Foxp3 work is candidate-locus ChIP; FECR1 is CasIP of promoter RNAs; Yoruba data are 27K methylation arrays. Treating them as one ChIP-seq method overstates shared technology.

    Evidence for the claim as stated.

  • SupportsChIP-seqmethod

    What 'epigenetic activation' means also disagrees. Rice Kcr occupancy resembles acetylation and moves with metabolic stress but is not proven necessary at each site. FECR1 recruits TET1/DNMT1 logic at FLI1. Foxp3 stability tracks TSDR demethylation rather than a mapped histone peak. Those are different causal sketches.

    Evidence for the claim as stated.

Open questions

Tensions this paper is part of

From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.

Related papers in this topic

Same topic cluster — not a recommendation engine.