Genome-wide binding sites of FOSL1, FOSL2 and BATF in human Th17 cells [ChIP-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA731664 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14611532_1.fastq.gz | Fastqsanger.gz | |||
| SRR14611532_2.fastq.gz | Fastqsanger.gz | |||
| SRR14611533_1.fastq.gz | Fastqsanger.gz | |||
| SRR14611533_2.fastq.gz | Fastqsanger.gz | |||
| SRR14611534_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:The aim of this study was to investigate the transciptional mechanisms governed by FOSL1, FOSL2 and BATF for regulation of human Th17 cell-function. To determine the genome-wide binding sites of these factors, ChIP-seq analysis was performed using in vitro derived Th17 cells at 72h of polarization.
2022-04-12 | GSE174810 | GEO
Project description:The differentiation of Th17 cells is controlled by a complex network of transcription factors (TFs), including FOS and JUN proteins of the AP-1 family. The FOS-like proteins, FOSL1 and FOSL2 have recently been reported to control Th17 responses. The molecular mechanisms dictating their roles, however, are unclear. Moreover, although the functions of AP-1 TFs are largely governed by their protein-protein interactions, these are also poorly characterized in this milieu. Using affinity purification in combination with mass-spectrometry we established the first interactomes of FOSL1 and FOSL2 in human Th17 cells. In addition to their known interactions with JUN proteins, our analysis identified several novel binding partners of FOSL factors. Gene ontology analysis revealed RNA binding was enriched as the major functionality for FOSL1 and FOSL2 associated proteins, thereby suggesting possible mechanistic links that have not been studied before. Intriguingly, 29 interactors were found to be shared between FOSL1 and FOSL2, which included crucial regulators of Th17-fate. These findings, including unique and shared interactions, were validated using parallel reaction monitoring targeted mass-spectrometry (PRM-MS), with additional measurements with other laboratory methods. Overall, this study provides key insights into interaction-based signalling mechanisms of FOSL1 and FOSL2, which potentially control Th17 cell-development and associated pathologies.
2021-11-02 | PXD025729 | Pride
Project description:The aim of this study was to investigate the transciptional mechanisms governed by FOSL1, FOSL2 and BATF for regulation of human Th17 cell-function. FOSL factors were transiently perturbed using RNAi (KD) and over-expression (OE) strategies, whereas BATF was perturbed using RNAi only. RNA-seq was then performed to determine their global transciptional targets.
2022-04-12 | GSE174809 | GEO
Project description:Global gene-regulatory targets and Genome-wide binding sites of FOSL1, FOSL2 and BATF in human Th17 cells
| PRJNA734773 | ENA
Project description:Global gene-regulatory targets of FOSL1, FOSL2 and BATF in human Th17 cells [RNA-seq]
| PRJNA731665 | ENA
Project description:The differentiation of Th17 cells is controlled by a complex network of transcription factors (TFs), including FOS and JUN proteins of the AP-1 family. The FOS-like proteins, FOSL1 and FOSL2 have recently been reported to control Th17 responses. The molecular mechanisms dictating their roles, however, are unclear. Moreover, although the functions of AP-1 TFs are largely governed by their protein-protein interactions, these are also poorly characterized in this milieu.
Using affinity purification in combination with mass-spectrometry we established the first interactomes of FOSL1 and FOSL2 in human Th17 cells. In addition to their known interactions with JUN proteins, our analysis identified several novel binding partners of FOSL factors. Gene ontology analysis revealed RNA binding was enriched as the major functionality for FOSL1 and FOSL2 associated proteins, thereby suggesting possible mechanistic links that have not been studied before. Intriguingly, 29 interactors were found to be shared between FOSL1 and FOSL2, which included crucial regulators of Th17-fate. These findings, including unique and shared interactions, were validated using parallel reaction monitoring targeted mass-spectrometry (PRM-MS), with additional measurements with other laboratory methods. Overall, this study provides key insights into interaction-based signalling mechanisms of FOSL1 and FOSL2, which potentially control Th17 cell-development and associated pathologies
2021-09-18 | PXD025840 | panorama
Project description:Th17 cells are essential for protection against extracellular pathogens, but their aberrant activity can cause autoimmunity. Molecular mechanisms that dictate Th17 cell-differentiation have been extensively studied using mouse models. However, species-specific differences underscore the need to validate these findings in human. Here, we characterized the human-specific roles of three AP-1 transcription factors, FOSL1, FOSL2 and BATF, during early stages of Th17 differentiation. Our results demonstrate that FOSL1 and FOSL2 co-repress Th17 fate-specification, whereas BATF promotes the Th17 lineage. Strikingly, FOSL1 was found to play different roles in human and mouse. Genome-wide binding analysis indicated that FOSL1, FOSL2 and BATF share occupancy over regulatory regions of genes involved in Th17 lineage commitment. These AP-1 factors also share their protein interacting partners, which suggests mechanisms for their functional interplay. Our study further reveals that the genomic binding sites of FOSL1, FOSL2 and BATF harbour hundreds of autoimmune disease-linked SNPs. We show that many of these SNPs alter the ability of these transcription factors to bind DNA. Our findings thus provide critical insights into AP-1-mediated regulation of human Th17-fate and associated pathologies.
| S-EPMC9122603 | biostudies-literature
Project description:Th17 cells secrete IL-17A, IL-17F, IL-21, and IL-22 cytokines that are critical in mediating inflammation and protecting the host from microorganisms infection. The basic leucine zipper transcription factor ATF-like (Batf) contributes to the transcriptional programming of multiple effector T cells, and is required for Th17 cell development. Here, we have interrogated mechanisms by which Batf promotes and stabilizes Th17 cell phenotype. We have shown that in vitro differentiated Th17 cells have increased expression of Th1 and Treg signature genes in the absence of Batf. In addition, Citrobacter rodentium infected Batf-deficient (Batf KO) mice fail to clear the infection, and that is correlated with diminished IL-17A and IL-22 cytokine production and increased Foxp3 and Ifng expression compared to WT mice. We find that Batf sustains Th17 phenotype in long-term culture conditions by suppressing Th1- and Treg-specific gene expression. Mechanistically, we reveal that Batf negatively regulates IL-2-STAT5 signaling and modulates STAT5 binding at the Ifng and Foxp3 gene loci thus suppressing Th1-Treg phenotype in Th17 cell development. Inhibition of STAT5 DNA binding activity in Batf KO Th17 cells was able to repress Ifng and Foxp3 expression compared to control-treated cells. Moreover, STAT5 cooperates with transcription factors Ets1 and Runx1 to mediate epigenetic modification and regulate gene expression. Thus, our study has revealed an essential function of Batf in modulating the IL-2-STAT5 signaling to promote and stabilize Th17 cell development.
2023-04-26 | GSE167417 | GEO
Project description:Th17 cells secrete IL-17A, IL-17F, IL-21, and IL-22 cytokines that are critical in mediating inflammation and protecting the host from microorganisms infection. The basic leucine zipper transcription factor ATF-like (Batf) contributes to the transcriptional programming of multiple effector T cells, and is required for Th17 cell development. Here, we have interrogated mechanisms by which Batf promotes and stabilizes Th17 cell phenotype. We have shown that in vitro differentiated Th17 cells have increased expression of Th1 and Treg signature genes in the absence of Batf. In addition, Citrobacter rodentium infected Batf-deficient (Batf KO) mice fail to clear the infection, and that is correlated with diminished IL-17A and IL-22 cytokine production and increased Foxp3 and Ifng expression compared to WT mice. We find that Batf sustains Th17 phenotype in long-term culture conditions by suppressing Th1- and Treg-specific gene expression. Mechanistically, we reveal that Batf negatively regulates IL-2-STAT5 signaling and modulates STAT5 binding at the Ifng and Foxp3 gene loci thus suppressing Th1-Treg phenotype in Th17 cell development. Inhibition of STAT5 DNA binding activity in Batf KO Th17 cells was able to repress Ifng and Foxp3 expression compared to control-treated cells. Moreover, STAT5 cooperates with transcription factors Ets1 and Runx1 to mediate epigenetic modification and regulate gene expression. Thus, our study has revealed an essential function of Batf in modulating the IL-2-STAT5 signaling to promote and stabilize Th17 cell development.
2023-04-26 | GSE167418 | GEO
Project description:Th17 cells have critical roles in mucosal defense and are major contributors to inflammatory disease. Their differentiation requires the nuclear hormone receptor RORγt working with multiple other essential transcription factors (TFs). We have used an iterative systems approach, combining genome-wide TF occupancy, expression profiling of TF mutants, and expression time series to delineate the Th17 global transcriptional regulatory network. We find that cooperatively-bound BATF and IRF4 contribute to initial chromatin accessibility, and with STAT3 initiate a transcriptional program that is then globally tuned by the lineage-specifying TF RORγt, which plays a focal deterministic role at key loci. Integration of multiple datasets allowed inference of an accurate predictive model that we computationally and experimentally validated, identifying multiple new Th17 regulators, including Fosl2, a key determinant of cellular plasticity. This interconnected network can be used to investigate new therapeutic approaches to manipulate Th17 functions in the setting of inflammatory disease. 143 RNA-seq, 83 ChIP-seq, 65 ChIP-seq controls, and 16 FAIRE-seq
2012-09-20 | E-GEOD-40918 | biostudies-arrayexpress