ArticleImmunity2022
The transcription factor FoxP3 can fold into two dimerization states with divergent implications for regulatory T cell function and immune homeostasis.
Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- Avian Foxp3 acts as a switch for IL-10 by directly binding the T3G motif: revealing a novel epigenetic modulation paradigm.Cell communication and signaling : CCS · 2026Article
- Transcription factors remodel tumor immune microenvironment by impacting multiple immune cells.Discover oncology · 2026Review
- A Fkh1/2 binding site array in the WHI5 promoter drives sub-scaling transcription.Cell reports · 2026Article
- Multimerizing transcription factors FOXP3 and AIRE as chromatin architectural regulators.Nature immunology · 2026Review
- FOXC2 represses NFAT1-dependent transcription through a DNA-facilitated protein-protein interaction.Nucleic acids research · 2026Article
- Review
- FoxP3 forms a head-to-head dimer in vivo and stabilizes its multimerization on adjacent microsatellites.Cell reports · 2025Article
- Inborn errors of regulatory T-cell differentiation and function.The Journal of allergy and clinical immunology · 2025Review
- Missense variants in human forkhead transcription factors reveal determinants of forkhead DNA bispecificity.Cell reports · 2025Article
- Review
- A Fkh1/2 binding site array in thebioRxiv : the preprint server for biology · 2025Article
- FoxP3 forms a head-to-head dimer in vivo and stabilizes its multimerization on adjacent microsatellites.bioRxiv : the preprint server for biology · 2025Article
- Missense variants in human forkhead transcription factors reveal determinants of forkhead DNA bispecificity.bioRxiv : the preprint server for biology · 2025Article
- Ultrastable and versatile multimeric ensembles of FoxP3 on microsatellites.Molecular cell · 2025Article
- Footprint-C reveals transcription factor modes in local clusters and long-range chromatin interactions.Nature communications · 2024Article
- Dynamic Foxp3-chromatin interaction controls tunable Treg cell function.The Journal of experimental medicine · 2024Article
- Deubiquitinating enzymes: potential regulators of the tumor microenvironment and implications for immune evasion.Cell communication and signaling : CCS · 2024Review
- DNA bridging of FOXP3 ladder-like multimer: Unveiling a novel transcriptional regulation paradigm.Innovation (Cambridge (Mass.)) · 2024Review
- DNA controls the dimerization of the human FoxP1 forkhead domain.Cell reports. Physical science · 2024Article
- Elusive modes of Foxp3 activity in versatile regulatory T cells.Frontiers in immunology · 2024Review
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
FoxP3 is an essential transcription factor (TF) for immunologic homeostasis, but how it utilizes the common forkhead DNA-binding domain (DBD) to perform its unique function remains poorly understood. We here demonstrated that unlike other known forkhead TFs, FoxP3 formed a head-to-head dimer using a unique linker (Runx1-binding region [RBR]) preceding the forkhead domain. Head-to-head dimerization conferred distinct DNA-binding specificity and created a docking site for the cofactor Runx1. RBR was also important for proper folding of the forkhead domain, as truncation of RBR induced domain-swap dimerization of forkhead, which was previously considered the physiological form of FoxP3. Rather, swap-dimerization impaired FoxP3 function, as demonstrated with the disease-causing mutation R337Q, whereas a swap-suppressive mutation largely rescued R337Q-mediated functional impairment. Altogether, our findings suggest that FoxP3 can fold into two distinct dimerization states: head-to-head dimerization representing functional specialization of an ancient DBD and swap dimerization associated with impaired functions.
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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.