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FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE286473 | GEO | 2025/11/13

REPOSITORIES: GEO

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Cis-Regulatory Element and Transcription Factor Circuitry Required for Cell-Type Specific Expression of FOXP3.

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FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry [CRISPRi]

Project description: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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FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry [mouse_Tconv_ChIP-seq]

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Project description:FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry

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FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry [CRISPRi]

Project description:FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry [CRISPRi]

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