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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 13, 2025 |
| Title |
FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry [CRISPRKO] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
FOXP3 is a lineage-defining transcription factor (TF) for immune-suppressive regulatory T cells (Tregs). While mice exclusively express FOXP3 in Tregs, humans also transiently express FOXP3 in stimulated conventional CD4+ T cells (Tconvs). Mechanisms governing these distinct expression patterns remain unknown. Here, we performed CRISPR screens tiling the FOXP3 locus and targeting TFs in human Tregs and Tconvs to discover cis-regulatory elements (CREs) and trans-regulators of FOXP3. Tconv FOXP3 expression depended on a subset of Treg CREs and Tconv-selective positive (TcNS+) and negative (TcNS-) CREs. Combinatorial silencing of Tconv CREs revealed their epistatic logic. The CREs are occupied and regulated by TFs we identified as critical regulators of FOXP3. Finally, mutagenesis of murine TcNS- revealed that it is critical for restriction of FOXP3 expression to Tregs. We discover CRE and TF circuitry controlling FOXP3 expression and reveal evolution of mechanisms regulating a gene indispensable to immune homeostasis.
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| Overall design |
Pooled CRISPR screens in human regulatory T cells (Tregs) and conventional T cells (Tconvs). The CRISPR KO TF library targets transcription factors and select chromatin modifiers and immune genes of interest. Tconv screens were conducted in 3 donors. Treg screens were conducted in 2 donors.
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| Contributor(s) |
Umhoefer JM, Arce MM, Kasinathan S, Whalen S, Dajani R, Subramanya S, Goudy L, Belk JA, Zhou R, N Pham MT, Zhang W, Hernandez R, Tran C, Kirthivasan N, Freimer JW, Mowery CT, Nguyen V, Ota M, Gowen BG, Simeonov DR, Curie GL, Li Z, Chen AY, Corn JE, Chang HY, Tang Q, Gilbert LA, Satpathy AT, Pollard KS, Marson A |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jan 12, 2025 |
| Last update date |
Nov 13, 2025 |
| Contact name |
Alexander Marson |
| E-mail(s) |
alexander.marson@ucsf.edu
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| Organization name |
UCSF Gladstone Institutes
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| Street address |
1650 Owens St.
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (10)
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| GSM8728218 |
Tconv FOXP3 low bin, Donor 1, CRISRP KO TF screen |
| GSM8728219 |
Tconv FOXP3 high bin, Donor 1, CRISRP KO TF screen |
| GSM8728220 |
Tconv FOXP3 low bin, Donor 2, CRISRP KO TF screen |
| GSM8728221 |
Tconv FOXP3 high bin, Donor 2, CRISRP KO TF screen |
| GSM8728222 |
Tconv FOXP3 low bin, Donor 3, CRISRP KO TF screen |
| GSM8728223 |
Tconv FOXP3 high bin, Donor 3, CRISRP KO TF screen |
| GSM8728224 |
Treg FOXP3 low bin, Donor 1, CRISRP KO TF screen |
| GSM8728225 |
Treg FOXP3 high bin, Donor 1, CRISRP KO TF screen |
| GSM8728226 |
Treg FOXP3 low bin, Donor 2, CRISRP KO TF screen |
| GSM8728227 |
Treg FOXP3 high bin, Donor 2, CRISRP KO TF screen |
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| This SubSeries is part of SuperSeries: |
| GSE286473 |
FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry |
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| Relations |
| BioProject |
PRJNA1209553 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE286470_Combined_gene_summary.xlsx |
273.3 Kb |
(ftp)(http) |
XLSX |
| GSE286470_Combined_grna_summary.xlsx |
1.6 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
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