Characterization of transcriptional and epigenetic changes during mouse alternative macrophage polarization
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE106706 | GEO | 2017/11/10
SECONDARY ACCESSION(S): PRJNA417710
REPOSITORIES: GEO
Similar Datasets
Project description:The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, however our understanding remains limited regarding the molecular determinants of repression. Here we showed that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during mouse alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300 coactivator and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation and chromatin accessibility. In addition, STAT6-repressed enhancers showed extensive overlap with the NF-κB p65 transcription factor cistrome and exhibited decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes.
2017-11-10 | GSE106703 | GEO
Project description:The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, however our understanding remains limited regarding the molecular determinants of repression. Here we showed that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during mouse alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300 coactivator and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation and chromatin accessibility. In addition, STAT6-repressed enhancers showed extensive overlap with the NF-κB p65 transcription factor cistrome and exhibited decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes.
2017-11-10 | GSE106702 | GEO
Project description:The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, however our understanding remains limited regarding the molecular determinants of repression. Here we showed that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during mouse alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300 coactivator and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation and chromatin accessibility. In addition, STAT6-repressed enhancers showed extensive overlap with the NF-κB p65 transcription factor cistrome and exhibited decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes.
2017-11-10 | GSE106700 | GEO
Project description:The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, however our understanding remains limited regarding the molecular determinants of repression. Here we showed that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during mouse alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300 coactivator and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation and chromatin accessibility. In addition, STAT6-repressed enhancers showed extensive overlap with the NF-κB p65 transcription factor cistrome and exhibited decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes.
2017-11-10 | GSE106705 | GEO
Project description:The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, however our understanding remains limited regarding the molecular determinants of repression. Here we showed that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during mouse alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300 coactivator and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation and chromatin accessibility. In addition, STAT6-repressed enhancers showed extensive overlap with the NF-κB p65 transcription factor cistrome and exhibited decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes.
2017-11-10 | GSE106704 | GEO
Project description:The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, however our understanding remains limited regarding the molecular determinants of repression. Here we showed that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during mouse alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300 coactivator and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation and chromatin accessibility. In addition, STAT6-repressed enhancers showed extensive overlap with the NF-κB p65 transcription factor cistrome and exhibited decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes.
2017-11-10 | GSE106701 | GEO
Project description:Characterization of transcriptional and epigenetic changes during mouse alternative macrophage polarization
| PRJNA417710 | ENA
Project description:Macrophages (MФ) are an essential immune cell for defense and repair that travel to different tissues and adapt based on local stimuli. A critical factor that may govern their polarization is the crosstalk between metabolism and epigenetics. However, simultaneous measurements of metabolites, epigenetics, and proteins (phenotype) have been a major technical challenge. To address this, we have developed a novel triomics approach using mass spectrometry to comprehensively analyze metabolites, proteins, and histone modifications in a single sample. To demonstrate this technique, we investigated the metabolic-epigenetic-phenotype axis following polarization of human blood-derived monocytes into either 'proinflammatory M1-' or 'anti-inflammatory M2-' MФs. We report here a complex relationship between arginine, tryptophan, glucose, and the citric acid cycle metabolism, protein and histone post-translational modifications, and human macrophage polarization that was previously not described. Surprisingly, M1-MФs had globally reduced histone acetylation levels but high levels of acetylated amino acids. This suggests acetyl-CoA was diverted, in part, toward acetylated amino acids. Consistent with this, stable isotope tracing of glucose revealed reduced usage of acetyl-CoA for histone acetylation in M1-MФs. Furthermore, isotope tracing also revealed MФs uncoupled glycolysis from the tricarboxylic acid cycle, as evidenced by poor isotope enrichment of succinate. M2-MФs had high levels of kynurenine and serotonin, which are reported to have immune-suppressive effects. Kynurenine is upstream of de novo NAD+ metabolism that is a necessary cofactor for Sirtuin-type histone deacetylases. Taken together, we demonstrate a complex interplay between metabolism and epigenetics that may ultimately influence cell phenotype.
| S-EPMC9525912 | biostudies-literature
Project description:Macrophages belong to a special phagocytic subgroup of human leukocytes and are one of the important cells of the human immune system. They participate in both specific and innate immune processes and play an important role in the host's resistance to pathogen invasion and the inflammatory response. Small noncoding RNAs are a group of small RNA molecules that can be transcribed without the ability to encode proteins but could play a specific function in cells. We used high-throughput sequencing analysis and qPCR to detect the expression changes of the small noncoding RNAome during macrophage polarization.
2022-03-19 | GSE198744 | GEO
Project description:Macrophages belong to a special phagocytic subgroup of human leukocytes and are one of the important cells of the human immune system. Small noncoding RNAs are a group of small RNA molecules that can be transcribed without the ability to encode proteins but could play a specific function in cells. SncRNAs mainly include microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs) and repeat RNAs. We used high-throughput sequencing analysis and qPCR to detect the expression changes of the small noncoding RNAome during macrophage polarization. Our results showed that 84 miRNAs and 47 miRNAs with were downregulated during M1 macrophage polarization and that 11 miRNAs were upregulated and 19 miRNAs were downregulated during M2 macrophage polarization. MiR-novel-3-nature and miR-27b-5p could promote expression of TNF-α which was marker gene of M1 macrophages. The piRNA analysis results showed that 69 piRNAs were upregulated and 61 piRNAs were downregulated during M1 macrophage polarization and that 3 piRNAs were upregulated and 10 piRNAs were downregulated during M2 macrophage polarization. DQ551351 and DQ551308 could promote the mRNA expression of TNF-α and DQ551351overexpression promoted the antitumor activity of M1 macrophages. SnoRNA results showed that 62 snoRNAs were upregulated and 59 snoRNAs were downregulated during M1 macrophage polarization, whereas 6 snoRNAs were upregulated and 10 snoRNAs were downregulated during M2 macrophage polarization. Overexpression of snoRNA ENSMUST00000158683.2 could inhibit expression of TNF-α. For snRNA, we found that 12 snRNAs were upregulated and 15 snRNAs were downregulated during M1 macrophage polarization and that 2 snRNAs were upregulated during M2 macrophage polarization. ENSMUSG00000096786 could promote expression of IL-1 and iNOS and ENSMUSG00000096786 overexpression promoted the antitumor activity of M1 macrophages. Analysis of repeat RNAs showed that 7 repeat RNAs were upregulated and 9 repeat RNAs were downregulated during M1 macrophage polarization and that 2 repeat RNAs were downregulated during M2 macrophage polarization. We first reported the expression changes of piRNA, snoRNA, snRNA and repeat RNA during macrophage polarization, and preliminarily confirmed that piRNA, snoRNA and snRNA can regulate the function of macrophages.
| S-EPMC9127141 | biostudies-literature