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Status |
Public on May 28, 2024 |
Title |
Dynamic Foxp3-chromatin interaction controls tunable Treg cell function [Cut&Run Foxp3 Batf] |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Nuclear factor Foxp3 determines regulatory T (Treg) cell fate and function via mechanisms that remain unclear. Here we investigate the nature of Foxp3-mediated gene regulation in suppressing autoimmunity and antitumor immune response. Contrasting with previous models, we find that Foxp3-chromatin binding is regulated by Treg activation states, tumor microenvironment, and antigen and cytokine stimulations. Proteomics studies uncovered dynamic proteins within the Foxp3 proximity upon TCR or IL-2 receptor signaling in vitro, reflecting intricate interactions among Foxp3, signal transducers, and chromatin. Pharmacological inhibition and genetic knockdown experiments indicate that NFAT and AP-1 protein Batf are required for enhanced Foxp3-chromatin binding in activated Treg cells and tumor-infiltrating Treg cells to modulate target gene expression. Furthermore, mutations at Foxp3 DNA-binding domain destabilize Foxp3-chromatin association. These representative settings delineate context-dependent Foxp3-chromatin interaction, suggesting that Foxp3 associates with chromatin by hijacking DNA-binding proteins resulting from Treg activation or differentiation, which is stabilized by direct Foxp3-DNA binding, to dynamically regulate Treg cell function according to immunological contexts.
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Overall design |
Cut&Run protocol were performed to detect Batf binding sites changed in various settings. Each have 2 replicates.
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Contributor(s) |
He M, Zong X, Xu B, Feng Y |
Citation(s) |
38935023 |
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Submission date |
Oct 11, 2023 |
Last update date |
Aug 27, 2024 |
Contact name |
Beisi Xu |
E-mail(s) |
beisi.xu@stjude.org
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Organization name |
St Jude Children's Research Hosipital
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Department |
Center for Applied Bioinformatics
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Street address |
262 Danny Thomas Pl
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City |
Memphis |
State/province |
Tennessee |
ZIP/Postal code |
38105 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (12)
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This SubSeries is part of SuperSeries: |
GSE149674 |
Dynamic Foxp3-chromatin interaction controls tunable Treg cell function |
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Relations |
BioProject |
PRJNA1026939 |