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Series GSE245100 Query DataSets for GSE245100
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
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.
 
Overall design Cut&Run protocol were performed to detect Batf binding sites changed in various settings. Each have 2 replicates.
 
Contributor(s) He M, Zong X, Xu B, Feng Y
Citation(s) 38935023
Submission date Oct 11, 2023
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 (12)
GSM7836319 2523655_CR_Batf_rTreg_1
GSM7836320 2523656_CR_Batf_rTreg_2
GSM7836321 2523657_CR_Batf_aTreg_1
This SubSeries is part of SuperSeries:
GSE149674 Dynamic Foxp3-chromatin interaction controls tunable Treg cell function
Relations
BioProject PRJNA1026939

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE245100_RAW.tar 1.6 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA

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