Evidence map›Paper›PMID 41313681›Full record

ArticleCell reports2025

FoxP3 forms a head-to-head dimer in vivo and stabilizes its multimerization on adjacent microsatellites.

Fangwei Leng, Ryan Clark, Wenxiang Zhang, Thibault Viennet, Cuidie Wang, Haribabu Arthanari, Xi Wang, Sun Hur

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Fangwei LengHoward Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Institute of Immunology, Chinese Institutes for Medical Research, Capital Medical University, Beijing 100069, China.
Ryan ClarkHoward Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Wenxiang ZhangHoward Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Shanghai Institute of Immunology, Shanghai Jiaotong University, Shanghai 200025, China.
Thibault ViennetDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Chemistry and iNANO, Aarhus University, Aarhus, Denmark.
Cuidie WangInstitute of Immunology, Chinese Institutes for Medical Research, Capital Medical University, Beijing 100069, China.
Haribabu ArthanariDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Xi WangHoward Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: xi.wang2@childrens.harvard.edu.
Sun HurHoward Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: sun.hur@crystal.harvard.edu.

Funding

Mechanism of the transcription factor FoxP3 in regulatory T cell developmentR01AI180137 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI Sun Hur · 2024 to 2026
$2.4M
NIAID NIH HHS R01 AI180137
6 · The paper itself

Abstract

FoxP3, the master regulator of Tregs, employs two DNA-binding modes to recognize diverse DNA sequences. It multimerizes on long TnG repeats (n = 2-5) to bridge DNA segments and stabilize chromatin loops, and it forms head-to-head (H-H) dimers on inverted repeat forkhead motifs (IR-FKHM) without bridging DNA. Although genomic data confirm its multimeric role, in vivo evidence for H-H dimerization has been elusive. Here, unbiased pull-down sequencing uncovers a range of relaxed motifs that drive H-H dimerization, enabling systematic genome-wide analysis. We demonstrate that FoxP3 binds genomic DNA as both H-H dimers and multimers in Tregs, with H-H binding often seeding and stabilizing multimerization on adjacent TnG repeats-especially on shorter, suboptimal repeats. While multimerization is conserved across FoxP family members, H-H dimerization is unique to FoxP3 orthologs, conferred by its divergent accessory loop. This dual-mode strategy broadens FoxP3's sequence repertoire and enhances its architectural function in chromatin looping.

Indexed as

Forkhead Transcription FactorsMicrosatellite RepeatsProtein MultimerizationAnimalsChromatinDNAHumansMiceProtein BindingT-Lymphocytes, RegulatoryChromatinDNAForkhead Transcription FactorsFOXP3 protein, humanFoxp3 protein, mousechromatin loopCP: Molecular biologyFoxP3microsatellitemultimerizationregulatory T cellssimple tandem repeattranscription factorTreg

Identifiers

PMID41313681
PMCPMC12820563

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.