Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BATF-JUN is critical for IRF4-mediated transcription in T cells

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE39756 | GEO | 2012/09/18

SECONDARY ACCESSION(S): PRJNA171705

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

BATF-JUN is critical for IRF4-mediated transcription in T cells

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

SPIB and BATF provide alternate determinants of IRF4 occupancy in Diffuse Large B-cell Lymphoma linked to disease heterogeneity

Project description:ChIP-seq data for the transcription factors (TFs) IRF4, PU.1 and SPIB from the cell lines OCI-LY3, OCI-LY10 and H929, and BATF from the cell lines OCI-Ly3 and OCI-Ly10. In addition ChIP-seq for the TFs IRF4, PU.1 and SPIB from the cell line OCI-LY3 following transfections of scramble/SPIB-siRNA. ChIP-seq data for the transcription factors (TFs) IRF4, PU.1 and SPIB from the cell lines OCI-LY3, OCI-LY10 and H929, and BATF from the cell lines OCI-Ly3 and OCI-Ly10. In addition ChIP-seq for the TFs IRF4, PU.1 and SPIB from the cell line OCI-LY3 following transfections of scramble/SPIB-siRNA.

2014-06-03 | E-GEOD-56857 | biostudies-arrayexpress

SPIB and BATF provide alternate determinants of IRF4 occupancy in Diffuse Large B-cell Lymphoma linked to disease heterogeneity

2014-06-03 | GSE56857 | GEO

Batf pioneers the reorganization of chromatin in developing effector T cells via Ets1-dependent recruitment of Ctcf [ChIP-seq]

Project description:We have examined mechanisms by which Batf acts to initiate gene transcription in developing effector CD4 T cells. We find that in addition to its pioneering function, Batf controls developmentally regulated recruitment of the chromatin architectural factor, Ctcf, to promote chromatin looping that is associated with transcription of lineage-specific genes. The chromatin organizing actions of Batf are largely Ets1-dependent, which appears to be indispensable for the Batf-dependent recruitment of Ctcf. Moreover, most of the Batf-dependent sites to which Ctcf is recruited lie outside of Ap-1–Irf composite elements (AICEs), indicating that direct involvement of Batf-Irf complexes is not required. Thus, we have identified a cooperative role for Batf, Ets1 and Ctcf in chromatin reorganization that underpins transcriptional programming of effector T cells.

2019-11-04 | GSE123198 | GEO

Batf pioneers the reorganization of chromatin in developing effector T cells via Ets1-dependent recruitment of Ctcf [Hi-C]

2019-11-04 | GSE123208 | GEO

Batf pioneers the reorganization of chromatin in developing effector T cells via Ets1-dependent recruitment of Ctcf [ATAC-seq]

2019-11-04 | GSE123206 | GEO

C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [Illumina BeadChip]

Project description:Disease-causing mutations in genes encoding transcription factors (TF) are frequent in hematopoietic malignancies and might affect TF-interactions with respective DNA-binding motifs. Here, we report the characterization of a recurrent somatic mutation c.295T>C in the IRF4 gene in classic Hodgkin lymphoma (cHL) leading to a C99R exchange. IRF4-C99R is located in the center of the IRF4 alpha3-recognition helix contacting the DNA 5´-GAAA-3´ IRF consensus sequence. IRF4-C99R fundamentally alters IRF4 DNA-binding, combining loss-of-binding at canonical IRF motifs and neomorph gain-of-binding at canonical and non-canonical IRF composite elements (CEs), in particular AP-1-IRF-CEs (AICEs). In line, IRF4-C99R profoundly impairs IRF4-dependent plasma cell induction, and specifically up-regulates degenerate-AICE-dependent distinct cHL disease-characteristic genes. These data document an unprecedented mutation-induced shift of TF binding specificity and its impact for lymphoma pathogenesis and TF modulation.

2023-07-19 | GSE211913 | GEO

C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [ChIP-Seq]

2023-07-19 | GSE211443 | GEO

C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [DNase-Seq]

2023-07-19 | GSE211441 | GEO

C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [RNA-Seq]

2023-07-19 | GSE211444 | GEO