Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA384995 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5489200.fastq.gz | Fastqsanger.gz | |||
| SRR5489210_1.fastq.gz | Fastqsanger.gz | |||
| SRR5489210_2.fastq.gz | Fastqsanger.gz | |||
| SRR5489201.fastq.gz | Fastqsanger.gz | |||
| SRR5489211_1.fastq.gz | Fastqsanger.gz |
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Project description:Mechanisms by which IFN-γ activates genes to promote macrophage activation are well studied, but little is known about mechanisms and functions of IFN-γ-mediated gene repression. We used an integrated transcriptomic and epigenomic approach to analyze chromatin accessibility, histone modifications, transcription factor binding, and gene expression in IFN-γ-primed human macrophages. IFN-γ suppressed basal expression of genes corresponding to an ‘M2’-like homeostatic/reparative phenotype. IFN-γ repressed genes by suppressing the function of enhancers enriched for binding by transcription factor MAF. Mechanistically, IFN-γ ‘disassembled’ a subset of enhancers by inducing coordinate suppression of binding by MAF, lineage-determining transcription factors, and chromatin accessibility. Genes associated with MAF-binding disassembled enhancers were suppressed in rheumatoid arthritis macrophages, revealing a disease-associated ‘negative IFN-γ signature’. These results identify enhancer inactivation and disassembly as a mechanism of IFN-γ-mediated gene repression, and MAF as a regulator of the macrophage enhancer landscape that is suppressed by IFN-γ to augment macrophage activation.
2017-07-01 | GSE98368 | GEO
Project description:Mechanisms by which IFN-γ activates genes to promote macrophage activation are well studied, but little is known about mechanisms and functions of IFN-γ-mediated gene repression. We used an integrated transcriptomic and epigenomic approach to analyze chromatin accessibility, histone modifications, transcription factor binding, and gene expression in IFN-γ-primed human macrophages. IFN-γ suppressed basal expression of genes corresponding to an ‘M2’-like homeostatic/reparative phenotype. IFN-γ repressed genes by suppressing the function of enhancers enriched for binding by transcription factor MAF. Mechanistically, IFN-γ ‘disassembled’ a subset of enhancers by inducing coordinate suppression of binding by MAF, lineage-determining transcription factors, and chromatin accessibility. Genes associated with MAF-binding disassembled enhancers were suppressed in rheumatoid arthritis macrophages, revealing a disease-associated ‘negative IFN-γ signature’. These results identify enhancer inactivation and disassembly as a mechanism of IFN-γ-mediated gene repression, and MAF as a regulator of the macrophage enhancer landscape that is suppressed by IFN-γ to augment macrophage activation.
2017-07-01 | GSE98367 | GEO
Project description:Mechanisms by which IFN-γ activates genes to promote macrophage activation are well studied, but little is known about mechanisms and functions of IFN-γ-mediated gene repression. We used an integrated transcriptomic and epigenomic approach to analyze chromatin accessibility, histone modifications, transcription factor binding, and gene expression in IFN-γ-primed human macrophages. IFN-γ suppressed basal expression of genes corresponding to an ‘M2’-like homeostatic/reparative phenotype. IFN-γ repressed genes by suppressing the function of enhancers enriched for binding by transcription factor MAF. Mechanistically, IFN-γ ‘disassembled’ a subset of enhancers by inducing coordinate suppression of binding by MAF, lineage-determining transcription factors, and chromatin accessibility. Genes associated with MAF-binding disassembled enhancers were suppressed in rheumatoid arthritis macrophages, revealing a disease-associated ‘negative IFN-γ signature’. These results identify enhancer inactivation and disassembly as a mechanism of IFN-γ-mediated gene repression, and MAF as a regulator of the macrophage enhancer landscape that is suppressed by IFN-γ to augment macrophage activation.
2017-07-01 | GSE98365 | GEO
Project description:IFN-γ Represses M2 Gene Expression in Human Macrophages by Suppressing and Disassembling MAF-binding Enhancers [ChIP-seq]
| PRJNA384909 | ENA
Project description:IFN-γ Represses M2 Gene Expression in Human Macrophages by Suppressing and Disassembling MAF-binding Enhancers [ATAC-seq]
| PRJNA384903 | ENA
Project description:To investigate c-Maf-controlled gene expression, M2-like bone marrow-derived macrophages (BMM) were transfected with c-Maf or control siRNA. Knockdown of c-Maf significantly decreased c-Maf protein and mRNA expression levels. In addition, IL-10 and arginase mRNA levels were significantly decreased while IL-12 was increased. In contrast, ectopic expression of c-Maf in the M1-like BMM significantly upregulated IL-10 and arginase mRNA expression levels while downregulated IL-12 expression level, suggesting an M2-like phenotype. These data indicate that c-Maf may be a critical controller in regulating M2-related gene expression. To further determine which part of the M2 macrophage transcriptomic profile is controlled by c-Maf, we performed microarray analysis using polarized M2-like BMM from WT or c-Maf KO fetal liver chimeric mice. Notably, many M2 genes were differentially regulated by c-Maf. Further real-time PCR (qPCR) analysis confirmed that the mRNA expression levels of IL-12, IL-1β, IL-6, arginase, IL-10, VEGF, TGF-β, IRF-4, and CCR2 were significantly altered in c-Maf-deficient M2 BMM. Since M2-like macrophages have a potent immunosuppressive function on T cell activation, we next determined whether deficiency of c-Maf in M2 BMM would reverse such effect. M2 BMM from WT mice exhibited potent immunosuppressive activity as IFN-γ production from antigen (Ag)-specific CD4 and CD8 T cells was significantly diminished. In contrast, c-Maf deficiency in M2 BMM significantly increased IFN-γ production by CD4 and CD8 T cells compared to WT M2 BMM. These data suggest that c-Maf not only controls many M2-related gene expression but also is critical in regulating M2-like macrophage-mediated T cell immunosuppression.
2020-04-17 | GSE139541 | GEO
Project description:Interferon-γ Represses M2 Gene Expression in Human Macrophages by Disassembling Enhancers Bound by the Transcription Factor MAF
| PRJNA384911 | ENA
Project description:Macrophages are known to be polarized into inflammatory (M1) and immunoregulatory (M2) cells when they are stimulated by agonists such as IFN-gamma and IL-4, respectively. If circulating monocytes may be polarized in response to T cell signals is often misguidedly deduced from macrophage results. Here the transcriptional responses of human CD14+ monocytes to IFN-gamma and IL-4 were analyzed using whole genome microarrays. A principal component analysis and hierarchical clustering showed that monocyte and macrophage responses were distinct. Monocytes stimulated with IFN-gamma and IL-4 for 6 hours exhibited some features of macrophage polarization. Indeed, when 80 genes considered as M1 and M2 genes were analyzed, we found that M1 genes were modulated in response to IFN-gamma and that M2 genes were modulated in response to IL-4. The M1 polarization of monocytes was transient because only M2 genes were modulated when monocytes were stimulated with IFN-gamma and IL-4 for 18 hours. However, the activation of monocytes by IFN-gamma and IL-4 could not be reduced to M1/M2 polarization status. Indeed, monocytes exhibited early specific signatures composed of 46 and 39 up-regulated genes in response to IFN-gamma and IL-4, respectively, and a late signature common to both molecules that consisted of 57 up-regulated genes. Taken together, these results demonstrated the extreme plasticity of human monocytes and suggested the existence of a core transcriptional termination program. Using early and late signatures might be pertinent to investigate monocyte activation in inflammatory or infectious diseases. Monocytes were stimulated with IFN-gamma (20ng/mL) or IL-4 (20ng/mL) for 6 and 18 hours or culture for 6 and 18 hours without agonist (Unstimulated samples). Monocytes-derived-macrophages (MDM) stimulated with IFN-gamma and IL-4 for 18 hours were used as controls. Each microarray is derived from a single biological sample.
2013-03-15 | E-GEOD-36537 | biostudies-arrayexpress
Project description:Macrophage activation is required for the control of innate and adaptive immune responses. The classification in M1 and M2 macrophages based on a combination of small numbers of membrane and soluble markers is operational in murine and human macrophages. If this classification may be extended to circulating monocytes is not elucidated. To answer such question, human monocytes were stimulated for 6 and 18 hours with IFN-gamma and IL-4, two canonical agonists of M1/M2 polarization in macrophages, and gene expression programs were investigated with whole genome microarrays. The temporal analysis of these programs showed marked differences to both IFN-gamma and IL-4. In 6-h stimulated monocytes, gene categories related to inflammatory and immune responses were enriched, and these monocytes exhibited a M1 and M2 polarization in response to IFN-gamma and IL-4, respectively, as found in macrophages. In 18-h stimulated monocytes, the categories related to innate immunity and metabolic pathways were enriched in response to IFN-gamma and IL-4, whereas PPAR signaling pathway was specifically enriched in response to IL-4. In addition, the M1 and M2 polarization induced by IFN-gamma and IL-4, respectively, was replaced by an original transcriptional program that did not depend on IFN-gamma and IL-4. This program appeared as networks around chemokines, NF-kappaB/MAP kinase pathways and MHC class II molecules. These results clearly demonstrated that monocyte activation consisted of an early polarized stage likely involved in effector responses and a delayed stage that may regulate host responses. The establishment of databases on human circulating monocytes using high throughput methods may be critical for pathophysiological and clinical non-invasive studies. Peripheral blood mononuclear cells (PBMCs) were isolated from leukopacks from normal blood donor buffy coats (Etablissement Français du Sang, Marseille, France) by Ficoll density gradient
2012-12-07 | E-GEOD-27658 | biostudies-arrayexpress
Project description:Macrophages are major effector cells and antigen presenting cells of the innate immune system and classical activation of macrophage function requires interferon–γ (IFN-γ) pretreatment (priming) and TLR stimuli, which promotes inflammatory responses though high levels of pro-inflammatory cytokines and lower level of the anti-inflammatory cytokines, resulting in microbicidal and tumoricidal effect. However, the underlying molecular mechanism of IFN-γ priming remains elusive. In this study, we explored the effect of IFN-γ on macrophages at miRNA level and discovered that miR-3473b, which was down-regulated after IFN-γ priming, could attenuate the priming effect of IFN-γ. Molecular study revealed that miR-3473b promoted Akt/GSK3 signaling and IL-10 production through directly targeting PTEN to suppress inflammatory response and tumor-suppressing capability of macrophages. In summary, our data demonstrate that IFN-γ beef up macrophage inflammatory response and tumor suppressing capacity by limiting miR-3473b-mediated PTEN suppression. Our work identified an IFN-γ/miR-3473b/Akt axis in the regulation of macrophage function and activation. the assay was performed with 5 μg total RNA samples from both normal BMM (labeled by Cy3) and BMM primed by IFN-γ (100U/ml) for 4 h(labeled by Cy5), normal BMM serves as control.
2014-10-01 | E-GEOD-50569 | biostudies-arrayexpress