Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA384909 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5487950.fastq.gz | Fastqsanger.gz | |||
| SRR5487960.fastq.gz | Fastqsanger.gz | |||
| SRR5487951.fastq.gz | Fastqsanger.gz | |||
| SRR5487961.fastq.gz | Fastqsanger.gz | |||
| SRR5487952.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 [ATAC-seq]
| PRJNA384903 | ENA
Project description:IFN-γ Represses M2 Gene Expression in Human Macrophages by Suppressing and Disassembling MAF-binding Enhancers [RNA-seq]
| PRJNA384995 | 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 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
Project description:Complete polarization of macrophages towards an M1-like proinflammatory and antimicrobial state requires combined action of IFN-γ and LPS. Synergistic activation of canonical inflammatory NF-κB target genes by IFN-γ and LPS is well appreciated, but less is known about whether IFN-γ negatively regulates components of the LPS response, and how this affects polarization. A combined transcriptomic and epigenomic approach revealed that IFN-γ selectively abrogates LPS-induced feedback and select metabolic pathways by suppressing TLR4-mediated activation of gene enhancers. In contrast to superinduction of inflammatory genes via enhancers that harbor IRF sequences and bind STAT1, IFN-γ-mediated repression targeted enhancers with STAT sequences that bound STAT3. TLR4-activated IFN-γ-suppressed enhancers comprised two subsets distinguished by differential regulation of histone acetylation and recruitment of STAT3, CDK8 and cohesin, and were functionally inactivated by IFN-γ. These findings reveal that IFN-γ suppresses feedback inhibitory and metabolic components of the TLR response to achieve full M1 polarization, and provide insights into mechanisms by which IFN-γ selectively inhibits TLR4-induced transcription.
2019-06-12 | GSE120944 | GEO
Project description:Complete polarization of macrophages towards an M1-like proinflammatory and antimicrobial state requires combined action of IFN-γ and LPS. Synergistic activation of canonical inflammatory NF-κB target genes by IFN-γ and LPS is well appreciated, but less is known about whether IFN-γ negatively regulates components of the LPS response, and how this affects polarization. A combined transcriptomic and epigenomic approach revealed that IFN-γ selectively abrogates LPS-induced feedback and select metabolic pathways by suppressing TLR4-mediated activation of gene enhancers. In contrast to superinduction of inflammatory genes via enhancers that harbor IRF sequences and bind STAT1, IFN-γ-mediated repression targeted enhancers with STAT sequences that bound STAT3. TLR4-activated IFN-γ-suppressed enhancers comprised two subsets distinguished by differential regulation of histone acetylation and recruitment of STAT3, CDK8 and cohesin, and were functionally inactivated by IFN-γ. These findings reveal that IFN-γ suppresses feedback inhibitory and metabolic components of the TLR response to achieve full M1 polarization, and provide insights into mechanisms by which IFN-γ selectively inhibits TLR4-induced transcription.
2019-06-12 | GSE120943 | GEO