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Series GSE149672 Query DataSets for GSE149672
Status Public on May 28, 2024
Title Dynamic Foxp3-chromatin interaction controls tunable Treg cell function [PSI-ChIP]
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 We developed a comparative proteomics method by projecting the spatial information (PSI) of nuclear proteins with peroxidase–mediated proximity ligation, thus revealing the protein components of the cis-regulatory elements bound by regulatory T cell lineage–specifying factor Foxp3. By incorporating this method with ChIP sequencing, we performed high efficient immunoprecipitation and ChIP sequencing.
 
Contributor(s) Zong X, Xu B, Cross R, Feng Y
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Submission date Apr 30, 2020
Last update date May 29, 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 (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
GSM4508695 1436476_Foxp3_PSI_1
GSM4508696 1436477_Foxp3_PSI_2
GSM4508697 1436478_Foxp3_PSI_3
This SubSeries is part of SuperSeries:
GSE149674 Dynamic Foxp3-chromatin interaction controls tunable Treg cell function
Relations
BioProject PRJNA629582
SRA SRP259375

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

Supplementary file Size Download File type/resource
GSE149672_RAW.tar 1.2 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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