ChIPseq analysis of IRF4 and BATF in immune cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Smita Agrawal
PROVIDER: E-GEOD-40727 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE40726: Transcriptional profiling of IRF4 -/- vs IRF4 +/- T-cells under Th17 polarizing conditions GSE40727: ChIPseq analysis of IRF4 and BATF in immune cells Refer to individual Series
2012-09-13 | E-GEOD-40483 | biostudies-arrayexpress
Project description:Purpose: The purpose of this study is to identify the genome-wide binding sites for IRF4 interaction partners PU.1, BATF, and JunB in dendritic cells. These ChIP-seq data were integrated with gene expression analysis in IRF4-sufficient and -deficient BMDCs in order to assemble an IRF4 gene regulatory network. Hematopoietic bone marrow progenitors from C57BL/6 mice were differentiated with GM-CSF and IL-4 for 5 days. On day 6, BMDCs were stimulated for 6 hours with 100ng/ml LPS. Fixed chromatin was immunoprecipitated with anti-PU.1, BATF, and JunB antibodies and subjected to high-throughput sequencing. The sequencing data for the input DNA was previously submitted as GSM999807.
2013-12-22 | E-GEOD-52772 | biostudies-arrayexpress
Project description:Purpose: The purpose of this study is to find the binding partner of IRF4 in the context of Th17- cell differentiation. To this end, we have used ChIPseq analysis followed by de novo motif search around genome-wide binding sites to identify BATF as the binding partner for IRF4 in the context of not only Th17 cells but other immune cell types as well.
2012-09-13 | GSE40727 | GEO
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
Project description:The transcription factor BATF is required for Th17 and TFH differentiation. Here, we show that BATF also has a fundamental role in regulating effector CD8+ T cell differentiation. BATF-deficient CD8+ T cells show profound defects in effector expansion and undergo proliferative and metabolic catastrophe early after antigen encounter. BATF, together with IRF4 and Jun proteins, binds to and promotes early expression of genes encoding lineage-specific transcription-factors (T-bet and Blimp-1) and cytokine receptors, while paradoxically repressing genes encoding effector molecules (IFNg and granzyme B). Thus, BATF amplifies TCR-dependent transcription factor expression and augments inflammatory signal propagation but restrains effector gene expression. This checkpoint prevents irreversible commitment to an effector fate until a critical threshold of downstream transcriptional activity has been achieved. This is an examination of 5 different transcription factors (TFs) with 5 different histone modifications in effector CD8+ T cells. Two of the TFs (BATF and IRF4) and the histone modifications were replicated. Appropriate control sequence files for ChIP input, IgG ChIP, and Total H3 are also included.
2014-03-02 | E-GEOD-54191 | biostudies-arrayexpress
Project description:IRF4 is critical for differentiation of various CD4+ effector T cells, such as T helper 1 (Th1), Th2, and Th17 subsets, through interaction with BATF-containing AP-1 heterodimers. A major BATF heterodimeric partner, JunB, regulates Th17 differentiation, but the role of JunB in other CD4+ effector T subsets is not fully understood. Here we demonstrate that JunB is essential for accumulation of Th1 and Th2 cells, as well as Th17 cells, both in vitro and in vivo. In mice immunized with lipopolysaccharide (LPS), papain, or complete Freund’s adjuvant (CFA), that induce predominantly Th1, Th2 and Th17 cells, respectively, accumulation of antigen-primed, Junb-deficient CD4+ T cells is significantly impaired. Loss of JunB decreases viability of cells activated under Th1-, Th2-, and Th17-polarizing conditions. RNA-sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) reveal that JunB directly regulates expression of various genes that are commonly induced in priming of naïve CD4+ T cells, including a pro-apoptotic gene Bcl2l11 (encoding Bim), and genes that are specifically induced in Th1, Th2, and Th17 cells. Furthermore, JunB colocalizes with BATF and IRF4 at genomic regions for approximately half of JunB direct target genes. Taken together, JunB, in collaboration with BATF and IRF4, serves a critical function in differentiation of diverse CD4+ T cells by controlling common and lineage-specific gene expression.
2021-10-01 | GSE172490 | GEO
Project description:The complex relationship between Th1 and Th17 cells is incompletely understood. The transcription factor T-bet is best known as the master regulator of Th1 lineage commitment. However, attention is now focused on the repression of alternate T cell subsets mediated by T-bet, particularly the Th17 lineage. Specifically it has recently been suggested that pathogenic Th17 cells express T-bet and are dependent on IL-23. However, T-bet has previously been shown to be a negative regulator of Th17 cells. We have taken an unbiased approach to determine the functional impact of T-bet on Th17 lineage commitment. Genome-wide analysis of functional T-bet binding sites provides an improved understanding of the transcriptional regulation mediated by T-bet, and suggests novel mechanisms by which T-bet regulates T helper cell differentiation. Specifically, we show that T-bet negatively regulates Th17 lineage commitment via direct repression of the transcription factor interferon regulatory factor-4 (IRF4). An in vivo analysis of the pathogenicity of T-bet deficient T cells demonstrated that Th17 responses were augmented in the absence of T-bet, and we have defined a critical temporal window for T-bet function. The interaction of the two key transcription factors T-bet and IRF4 during the determination of T cell fate choice significantly advances our understanding of the mechanisms underlying the development of pathogenic T cells. ChIP-seq analysis of T-bet in WT and Tbet -/- mice.
2013-12-03 | E-GEOD-40623 | biostudies-arrayexpress
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.
2012-09-18 | GSE39756 | GEO
Project description:We established whether partner transcription factor binding, chromatin structure, or gene expression is compromised upon loss of partner factors cdx2 or hnf4a in mouse intestinal villi. This metadata file describes the ChIP-seq componant of that data Intestinal epithelia were collected from mouse jejunum using EDTA-based chelation and ChIP-seq was performed, followed by next generation sequencing.
2013-02-05 | E-GEOD-34566 | biostudies-arrayexpress
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