Analyses of a mutant FoxP3 allele reveal BATF as a critical transcription factor in the differentiation and accumulation of tissue regulatory T cells
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ABSTRACT:
PROVIDER: PRJNA353077 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5010470.fastq.gz | Fastqsanger.gz | |||
| SRR5010471.fastq.gz | Fastqsanger.gz | |||
| SRR5010462.fastq.gz | Fastqsanger.gz | |||
| SRR5010472.fastq.gz | Fastqsanger.gz | |||
| SRR5010463.fastq.gz | Fastqsanger.gz |
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Project description:Mechanisms by which diverse transcription factors (TFs), particularly the master regulator Foxp3, shape the heterogeneous transcriptional and epigenetic landscape of regulatory T (Treg) cells remain poorly understood. Here, we discovered that Foxp3 cooperates with BATF to direct cis-regulatory programs and gene expression essential for differentiation of immunosuppressive effector Treg (eTreg) cells. Simultaneous single-cell chromatin accessibility and transcriptome profiling, combined with topic modeling, identified cis-regulatory elements and associated programs jointly regulated by these TFs in eTreg cells. Genome-wide mapping of Treg cell-specific BATF and eTreg cell-specific Foxp3 binding sites revealed their co-binding at some of these cis-elements, synergistically enhancing accessibility and transcription. Furthermore, we provide evidence that Foxp3 interacts with specific TFs to orchestrate diverse cis-regulatory programs among Treg cell differentiation states. Thus, Foxp3 serves as a master, but context-dependent regulator, cooperating with other TFs, including BATF, to shape the heterogeneous cis-regulatory and transcriptional landscape critical for functional Treg cell differentiation.
2026-03-31 | GSE267884 | GEO
Project description:Mechanisms by which diverse transcription factors (TFs), particularly the master regulator Foxp3, shape the heterogeneous transcriptional and epigenetic landscape of regulatory T (Treg) cells remain poorly understood. Here, we discovered that Foxp3 cooperates with BATF to direct cis-regulatory programs and gene expression essential for differentiation of immunosuppressive effector Treg (eTreg) cells. Simultaneous single-cell chromatin accessibility and transcriptome profiling, combined with topic modeling, identified cis-regulatory elements and associated programs jointly regulated by these TFs in eTreg cells. Genome-wide mapping of Treg cell-specific BATF and eTreg cell-specific Foxp3 binding sites revealed their co-binding at some of these cis-elements, synergistically enhancing accessibility and transcription. Furthermore, we provide evidence that Foxp3 interacts with specific TFs to orchestrate diverse cis-regulatory programs among Treg cell differentiation states. Thus, Foxp3 serves as a master, but context-dependent regulator, cooperating with other TFs, including BATF, to shape the heterogeneous cis-regulatory and transcriptional landscape critical for functional Treg cell differentiation.
2026-03-31 | GSE267882 | GEO
Project description:Mechanisms by which diverse transcription factors (TFs), particularly the master regulator Foxp3, shape the heterogeneous transcriptional and epigenetic landscape of regulatory T (Treg) cells remain poorly understood. Here, we discovered that Foxp3 cooperates with BATF to direct cis-regulatory programs and gene expression essential for differentiation of immunosuppressive effector Treg (eTreg) cells. Simultaneous single-cell chromatin accessibility and transcriptome profiling, combined with topic modeling, identified cis-regulatory elements and associated programs jointly regulated by these TFs in eTreg cells. Genome-wide mapping of Treg cell-specific BATF and eTreg cell-specific Foxp3 binding sites revealed their co-binding at some of these cis-elements, synergistically enhancing accessibility and transcription. Furthermore, we provide evidence that Foxp3 interacts with specific TFs to orchestrate diverse cis-regulatory programs among Treg cell differentiation states. Thus, Foxp3 serves as a master, but context-dependent regulator, cooperating with other TFs, including BATF, to shape the heterogeneous cis-regulatory and transcriptional landscape critical for functional Treg cell differentiation.
2026-03-31 | GSE306692 | GEO
Project description:Mechanisms by which diverse transcription factors (TFs), particularly the master regulator Foxp3, shape the heterogeneous transcriptional and epigenetic landscape of regulatory T (Treg) cells remain poorly understood. Here, we discovered that Foxp3 cooperates with BATF to direct cis-regulatory programs and gene expression essential for differentiation of immunosuppressive effector Treg (eTreg) cells. Simultaneous single-cell chromatin accessibility and transcriptome profiling, combined with topic modeling, identified cis-regulatory elements and associated programs jointly regulated by these TFs in eTreg cells. Genome-wide mapping of Treg cell-specific BATF and eTreg cell-specific Foxp3 binding sites revealed their co-binding at some of these cis-elements, synergistically enhancing accessibility and transcription. Furthermore, we provide evidence that Foxp3 interacts with specific TFs to orchestrate diverse cis-regulatory programs among Treg cell differentiation states. Thus, Foxp3 serves as a master, but context-dependent regulator, cooperating with other TFs, including BATF, to shape the heterogeneous cis-regulatory and transcriptional landscape critical for functional Treg cell differentiation.
2026-03-31 | GSE267881 | GEO
Project description:Mechanisms by which diverse transcription factors (TFs), particularly the master regulator Foxp3, shape the heterogeneous transcriptional and epigenetic landscape of regulatory T (Treg) cells remain poorly understood. Here, we discovered that Foxp3 cooperates with BATF to direct cis-regulatory programs and gene expression essential for differentiation of immunosuppressive effector Treg (eTreg) cells. Simultaneous single-cell chromatin accessibility and transcriptome profiling, combined with topic modeling, identified cis-regulatory elements and associated programs jointly regulated by these TFs in eTreg cells. Genome-wide mapping of Treg cell-specific BATF and eTreg cell-specific Foxp3 binding sites revealed their co-binding at some of these cis-elements, synergistically enhancing accessibility and transcription. Furthermore, we provide evidence that Foxp3 interacts with specific TFs to orchestrate diverse cis-regulatory programs among Treg cell differentiation states. Thus, Foxp3 serves as a master, but context-dependent regulator, cooperating with other TFs, including BATF, to shape the heterogeneous cis-regulatory and transcriptional landscape critical for functional Treg cell differentiation.
2026-04-29 | GSE267967 | GEO
Project description: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.
2024-05-28 | GSE245100 | GEO
Project description: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.
2024-05-29 | GSE268623 | GEO
Project description:Dynamic Foxp3-chromatin interaction controls tunable Treg cell function [Cut&Run Foxp3 Batf]
| PRJNA1026939 | ENA
Project description:Dynamic Foxp3-chromatin interaction controls tunable Treg cell function [Cut&Run Foxp3 Batf Ets1]
| PRJNA1117922 | ENA
Project description:Interferon regulatory factor 4 (IRF4) is an IRF family transcription factor with critical roles in lymphoid development and in regulating the immune response. IRF4 binds DNA weakly owing to a carboxy-terminal auto-inhibitory domain, but cooperative binding with factors such as PU.1 or SPIB in B cells increases binding affinity, allowing IRF4 to regulate genes containing ETS–IRF composite elements (EICEs; 5'-GGAAnnGAAA-3'). Here we show that in mouse CD4+ T cells, where PU.1/SPIB expression is low, and in B cells, where PU.1 is well expressed, IRF4 unexpectedly can cooperate with activator protein-1 (AP1) complexes to bind to AP1–IRF4 composite (5'-TGAnTCA/GAAA-3') motifs that we denote as AP1–IRF composite elements (AICEs). Moreover, BATF–JUN family protein complexes cooperate with IRF4 in binding to AICEs in pre-activated CD4+ T cells stimulated with IL-21 and in TH17 differentiated cells. Importantly, BATF binding was diminished in Irf4-/- T cells and IRF4 binding was diminished in Batf-/- T cells, consistent with functional cooperation between these factors. Moreover, we show that AP1 and IRF complexes cooperatively promote transcription of the Il10 gene, which is expressed in TH17 cells and potently regulated by IL-21. These findings reveal that IRF4 can signal via complexes containing ETS or AP1 motifs depending on the cellular context, thus indicating new approaches for modulating IRF4-dependent transcription. Genome-wide transcription factors mapping and binding of IRF4, BATF, IRF8, STAT3, JUN etc in WT, Irf4-/- and Batf-/- mice in different cell types (B cells, CD4+ T cells and TH17 cells) cultured with or without IL-21 was conducted. RNA-Seq is conducted in mouse B cells, CD4+ T cells, TH1/TH2/TH9/TH17/Treg.
2012-09-18 | E-GEOD-39756 | biostudies-arrayexpress