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| Status |
Public on May 29, 2024 |
| Title |
Dynamic Foxp3-chromatin interaction controls tunable Treg cell function [Cut&Run Foxp3 Batf Ets1] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| 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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| |
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| Overall design |
Cut&Run protocol were performed to detect Batf Ets1 or Foxp3 binding sites changed in various settings. Each have 2 or 3 replicates.
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| |
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| Contributor(s) |
He M, Zong X, Xu B, Feng Y |
| Citation(s) |
38935023 |
| |
| Submission date |
May 29, 2024 |
| Last update date |
Aug 27, 2024 |
| Contact name |
Beisi Xu |
| E-mail(s) |
beisi.xu@stjude.org
|
| Organization name |
St Jude Children's Research Hosipital
|
| Department |
Center for Applied Bioinformatics
|
| Street address |
262 Danny Thomas Pl
|
| City |
Memphis |
| State/province |
Tennessee |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE149674 |
Dynamic Foxp3-chromatin interaction controls tunable Treg cell function |
|
| Relations |
| BioProject |
PRJNA1117922 |
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