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Genome-wide identification of BATF2 binding sites in HeLa-BATF2 cells

ABSTRACT: Basic leucine zipper transcription factors (BATFs) play profound roles in the regulatory networks of gene expression in tumor cells. BATF2, also known as SARI (suppressor of AP-1, regulated by interferon), was able to suppress both growth and migration of various cancers. In searching for BATF2/SARI-specific regulatory DNA elements, we first established a stable BATF2 over-expression HeLa cell line, then employed ChIP-Sequencing in order to identify the responsive DNA motifs for BATF2/SARI.

ORGANISM(S): Homo sapiens

PROVIDER: GSE67258 | GEO | 2015/03/26

SECONDARY ACCESSION(S): PRJNA279358

REPOSITORIES: GEO

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Microarray analyses using bone marrow-derived macrophages from Batf2−/− and wildtype mice that had been stimulated with R848

Project description:We assessed the role of basic leucine zipper transcription factor ATF-like 2 (Batf2), particularly its positive transcriptional activities via TLR signals. Because TLR7 agonists are clinically used against tumors and have proven effective as antitumor drugs, we assessed effect of Batf2 on the responses to the TLR7 ligand (R848).

2017-07-24 | GSE101781 | GEO

Effect of Batf2 deficiency on gene epxression in murine alveolar macrophages treated ex vivo with IFNg and K. pneumoniae supernatant

Project description:Basic leucine zipper transcription factor ATF-like 2 (BATF2) is a transcription factor that is emerging as an important regulator of the innate immune system. We previously identified BATF2 among the top upregulated genes in human alveolar macrophages treated with LPS, but the signaling pathways that induce BATF2 expression in response to Gram-negative stimuli are incompletely understood. In addition, the role of BATF2 in the host response to pulmonary infection with a Gram-negative pathogen like Klebsiella pneumoniae (Kp) is not known. We show that induction of Batf2 gene expression in macrophages in response to Kp in vitro requires TRIF and type I interferon (IFN) signaling, but not MyD88 signaling. Analysis of the impact of BATF2-deficiency on macrophage effector functions in vitro showed that BATF2 does not directly impact macrophage phagocytic uptake and intracellular killing of Kp. However, BATF2 markedly enhanced macrophage pro-inflammatory gene expression and Kp-induced cytokine responses. In vivo, we observed that Batf2 gene expression was elevated in the lung tissue of wild type (WT) mice 24 h after pulmonary Kp infection, and Kp-infected BATF2-deficient (Batf2-/-) mice displayed a modest but significant increase in bacterial burden in the lung, spleen and liver compared to WT mice. WT and Batf2-/- mice showed similar recruitment of leukocytes following infection, but in line with our in vitro observations, pro-inflammatory cytokine levels in the alveolar space were reduced in Batf2-/- mice. Altogether, these results suggest that BATF2 enhances pro-inflammatory cytokine responses in macrophages in response to Kp, and that as such, BATF2 contributes to the host defense against pulmonary Kp infection.

2023-08-31 | GSE235114 | GEO

Loss of the immunomodulatory transcription factor BATF2 in humans is associated with a neurological phenotype

Project description:Epilepsy and mental retardation are known to be associated with pathogenic mutations of a broad range of genes that are expressed in the brain and play a role in neurodevelopment. Here, we report a family with three affected individuals whose clinical symptoms closely resemble a neurodevelopmental disorder. Whole-exome sequencing identified a homozygous stop-gain mutation p.Q19* in the BATF2 gene in the patients. The BATF2 transcription factor is predominantly expressed in macrophages and monocytes, and has been reported to modulate AP-1 transcription factor-mediated pro-inflammatory responses. Transcriptome analysis showed an altered base-level expression of interferon-stimulated genes in the patients’ blood, typical for type I interferonopathies. Peripheral blood mononuclear cells from all three patients demonstrated elevated responses to innate immune stimuli, which could be reproduced in CRISPR–Cas9-generated BATF2-/- human monocytic cell lines. BATF2 is, therefore, a novel disease-associated gene for severe epilepsy and mental retardation, related to dysregulation of immune responses, which underscores the relevance of neuroinflammation for epilepsy.

2023-01-25 | GSE220916 | GEO

Identification of genes up-regulated by the overexpression of HSF1 in human HeLa cells

Project description:To analyze target genes of human heat shock transcription factor 1 (HSF1), we first generated two independent HeLa clones (RDT1 and RDT2) expressing an actively mutated hHSF1 (hHSF1?RDT), which lacks the regulatory domain that masks its activation domain and possesses a glutamic acid at amino acid 395 instead of a leucine in the suppression domain of the trimerization domain (Fujimoto et al., J. Biol. Chem. 280, 34908-34916, 2005). We also generated a HeLa clone expressing chicken HSF1 (HeLa/cHSF1) to compare its profile of gene expression with those of RDT1 and RDT2 cells (Nakai and Morimoto, Mol. Cell. Biol. 13, 1983-1997, 1993). We then carried out DNA microarray analysis using total RNA isolated from HeLa, HeLa/cHSF1, RDT1, and RDT2 cells grown under normal growth conditions. mRNA levels in human HeLa, RDT1, RDT2, and HeLa/cHSF1 were analyzed by DNA microarray analysis using GeneChip Human Genome U133 Plus 2.0 Array (Affymetrix).

2010-09-22 | E-GEOD-19797 | biostudies-arrayexpress

Genome wide expession analysis of effect of Batf2 knock down in bone marrow derived macrophage cells stimulated with IFNg

Project description:Bmdm cells were differentiated for 10 days and harvested and culture in six well plate followed by transfection with Batf2 ShRNA. Media was replanished in every two days and on 10th day cells were stimulated with IFNg for 4 hrs. Total RNA was obtain after 4 hrs of stimulation. Total RNA was colloected from control ShRNA transfected Bmdm cells and Batf2 shRNA transfected Bmdm cells stimulated with/with out IFNg

2015-04-30 | E-GEOD-59209 | biostudies-arrayexpress

Genome-wide mapping of Fos binding site (K562)

Project description:Proto-oncogene c-Fos is a leucine-zipper containing transcription factor which has a DNA binding domain and a transactivation domain. Fos dimerizes with another transcription factor Jun to form AP1 transcription factor. The AP-1 complex has been implicated in transformation and progression of cancer. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

2009-12-31 | GSE19546 | GEO

Genome-wide mapping of Jun binding site (K562)

Project description:Proto-oncogene c-jun is a leucine-zipper containing transcription factor which has a DNA binding domain and a transactivation domain. Jun dimerizes with another transcription factor Fos to form AP1 transcription factor. The AP-1 complex has been implicated in transformation and progression of cancer. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

2009-12-31 | GSE19545 | GEO

Identification of genes up-regulated by the overexpression of HSF1 in human HeLa cells

Project description:To analyze target genes of human heat shock transcription factor 1 (HSF1), we first generated two independent HeLa clones (RDT1 and RDT2) expressing an actively mutated hHSF1 (hHSF1ΔRDT), which lacks the regulatory domain that masks its activation domain and possesses a glutamic acid at amino acid 395 instead of a leucine in the suppression domain of the trimerization domain (Fujimoto et al., J. Biol. Chem. 280, 34908-34916, 2005). We also generated a HeLa clone expressing chicken HSF1 (HeLa/cHSF1) to compare its profile of gene expression with those of RDT1 and RDT2 cells (Nakai and Morimoto, Mol. Cell. Biol. 13, 1983-1997, 1993). We then carried out DNA microarray analysis using total RNA isolated from HeLa, HeLa/cHSF1, RDT1, and RDT2 cells grown under normal growth conditions.

2010-09-22 | GSE19797 | GEO

A comprehensive analysis of gene expression patterns in wild-type and Batf2-/- bone marrow-derived macrophages (BMMφ)

Project description:We previously identified TLR-independent expression of 4933430F08Rik, encoding Batf2, in T. cruzi-infected bone marrow-derived dendritic cells (BMDCs) (Kayama et al., 2009). To determine the functions of Batf2 in innate immune responses, we performed a comprehensive gene expression analysis in wild-type and Batf2-/- bone marrow-derived macrophages (BMMφ). RNA-seq analysis showed that 98 genes are upregulated in Batf2-/- BMMφ stimulated with LPS following IFN-γ treatment, when compared with that in wild-type cells. Among these genes, we focused on Il23a, encoding IL-23p19, because IL-23 is able to promote expression of Il17a in Th17 cells.

2017-03-27 | GSE81724 | GEO

Genome-wide mapping of Jun binding site (K562)

2009-12-31 | E-GEOD-19545 | biostudies-arrayexpress

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