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Functional and cellular constraints that shaped the PPARg binding landscape in human and mouse macrophages

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE25137: Functional and cellular constraints that shaped the PPARg binding landscape in human and mouse macrophages: human expression GSE25426: Functional and cellular constraints that shaped the PPARg binding landscape in human and mouse macrophages: human ChIP-Seq Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Sebastian Pott

PROVIDER: E-GEOD-25608 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Functional and cellular constraints that shaped the PPARg binding landscape in human and mouse macrophages: human expression

Project description:Genome-wide comparisons of transcription factor binding sites in different species allow for a direct evaluation of the evolutionary constraints that shape transcription factor binding landscapes. To gain insights into the evolution of the PPARg-dependent transcriptional network we obtained binding data for PPARg, RXR and PU.1 in human macrophages and compared the profiles to matching data from mouse macrophages. We found that PPARg binding was highly divergent and only 5% of the PPARg bound regions were occupied in both species. Despite the low conservation of PPARg binding sites, conserved PPARg target genes contribute more than 30% to the functional target genes identified in human macrophages. In addition conserved target genes are strongly enriched for lipid metabolic functions. We detected the lineage-specification factor PU.1 at the majority of human PPARg binding sites. This confirmed the juxtaposed binding configuration found in mouse macrophages and demonstrated the preservation of tissue-specific adjacent PPARg-Pu.1 binding in the absence of individual binding site conservation. Finally, based on this of PPARg and PU.1 binding between human and mouse we suggest a mechanism by which PU.1 facilitates PPARg binding site turnover in macrophages. Comparison of RNAs level in Rosiglitazone (RSG) and vehicle (DMSO) treated PMA differentiated THP-1 cells over a timecourse from 0.5h to 12h

2011-12-01 | E-GEOD-25137 | biostudies-arrayexpress

Functional and cellular constraints that shaped the PPARg binding landscape in human and mouse macrophages: human ChIP-Seq

Project description:Genome-wide comparisons of transcription factor binding sites in different species allow for a direct evaluation of the evolutionary constraints that shape transcription factor binding landscapes. To gain insights into the evolution of the PPARg-dependent transcriptional network, we obtained binding data for PPARg, RXR and PU.1 in human macrophages and compared the profiles to matching data from mouse macrophages (Lefterova et al. 2010 (PMID 20176806); GSE21314). We found that PPARg binding was highly divergent and only 5% of the PPARg-bound regions were occupied in both species. Despite the low conservation of PPARg binding sites, conserved PPARg target genes contribute more than 30% to the functional target genes identified in human macrophages. In addition, conserved target genes are strongly enriched for lipid metabolic functions. We detected the lineage-specification factor PU.1 at the majority of human PPARg binding sites. This confirmed the juxtaposed binding configuration found in mouse macrophages and demonstrated the preservation of tissue-specific adjacent PPARg-Pu.1 binding in the absence of individual binding site conservation. Finally, based on this PPARg and PU.1 binding between human and mouse, we suggest a mechanism by which PU.1 facilitates PPARg binding site turnover in macrophages. Genome-wide location analysis for 3 transcription factors (PPARg, RXR and PU.1) in a human monocytic cell line (THP-1). This submission represents the human binding data component of the study.

2011-12-01 | E-GEOD-25426 | biostudies-arrayexpress

Functional and cellular constraints that shaped the PPARg binding landscape in human and mouse macrophages

Project description:Functional and cellular constraints that shaped the PPARg binding landscape in human and mouse macrophages

| PRJNA134257 | ENA

Homo sapiens

Project description:Functional and cellular constraints that shaped the PPARg binding landscape in human and mouse macrophages: human expression

| PRJNA142767 | ENA

Dose-dependent phorbol 12-myristate-13-acetate mediated monocyte-to-macrophage differentiation induces unique proteomic signatures in THP1 cells

Project description:Macrophages are sentinels of the immune system and THP1 monocytic cells are one of the widely used models to study immune responses in macrophages. Several monocyte-to-macrophage differentiation protocols exist with phorbol 12-myristate-13-acetate (PMA) being widely used and accepted. However, the concentrations and durations of PMA treatment to induce differentiation varies widely in published literature. In this study, we determined the proteome expression dynamics of THP1 macrophages differentiated from monocytes by three commonly used PMA-based differentiation protocols using dimethyl labeling-based quantitative proteomics analysis. Our analysis shows that variations in PMA concentration and varying periods of rest post-stimulation result in downstream differences in proteome expression and cellular processes. We demonstrate that these differences result in altered expression of cytokines upon stimulation with different TLR ligands. Together, these findings provide a valuable resource that significantly expands the knowledge of protein expression dynamics in in vitro models of macrophages which in turn has profound impact on the immune responses being studied.

2021-09-08 | PXD015872 | Pride

Homo sapiens

Project description:Functional and cellular constraints that shaped the PPARg binding landscape in human and mouse macrophages: human ChIP-Seq

| PRJNA142611 | ENA

Transcriptional effects of exogenous lipid on differentiated THP-1 cells

Project description:Lipid laden macrophages (LLM) can often be found in the airway and may indicate aspiration secondary to gastro-oesophageal reflux (GOR). GOR is often associated chronic inflammatory airways diseases. We therefore sought to determine whether lipid droplets from undigested or partially digested food had an effect on macrophage gene expression leading to bronchial inflammation. To test this, we generated an in vitro model using differentiated THP-1 cells which were treated with a high fat liquid feed. Gene expression, using the Agilent G4851C (v3) array, in phorbol myristate acetate (PMA) differentiated THP-1 cells was compared to undifferentiated cells and lipid treated differentiated THP-1 cells.

2017-05-02 | E-MTAB-4153 | biostudies-arrayexpress

RNA-seq of THP-1-derived macrophages infected with R. conorii and R. montanensis (1 hpi) against uninfected cells.

Project description:R. conorii (pathogenic) and R. montanensis (non-pathogenic) display opposite survival versus death phenotypes in macrophage-like cells, respectively. We herein employed a global transcriptomic profiling of host responses to infection (1hpi) of human THP-1 macrophages with R. conorii and R. montanensis. Shortly, total RNA was harvested from uninfected, R. conorii- and R. montanensis-infected THP-1 macrophages, DNA was removed from RNA purification (DNAse treatment), ribosomal RNA was depleted and cDNA libraries were constructed. The samples were sequenced using an Ion Proton V2 chip on Ion Chef Instrument. The programmes Cufflinks and Cuffmerge were used to map transcripts and calculate gene expression, and Cuffdiff was used to calculate which samples had genes, which were statistically significantly differentially expressed between conditions.

2019-12-01 | E-MTAB-6724 | biostudies-arrayexpress

Expression data from THP-1 cells and THP-1 cells stimulated with PMA

Project description:Macrophages play a key role in both innate and adaptive immunity, but our knowledge on the changes in transcription regulation that occurs during their differentiation from monocytes is still limited. In this study, we used a meta-analysis followed by a systems biology approach for the identification of differentially expressed genes between monocytes and macrophages and possible regulators of these changes in transcription. Based on the pattern of gene expression change, transcription regulator analysis predicted a decrease in Enhancer of Zeste homolog 2 (EZH2), a histone 3 lysine 27 methyl transferase, activity after differentiation of monocytes into macrophages. This inhibition was validated by a significant decrease in trimethylated H3K27 during differentiation of both human primary monocytes into macrophages and the THP-1 cell line into macrophage-like cells. Overexpressing EZH2 during differentiation of monocytes and THP-1 cells obstructs cellular adhesion, thus preventing the first step in differentiation. Another facet of macrophage differentiation is the cessation of proliferation, and inhibition of EZH2 by the small molecule inhibitor GSK126 in THP-1 cells indeed impedes proliferation. This study shows an important part for epigenetic changes during monocyte differentiation. It highlights the role of EZH2 activity behind the changes needed in adhesion and proliferation mechanisms for macrophage formation. THP-1s were differentiated into macrophage like cells by PMA stimulation.

2013-12-28 | E-GEOD-53691 | biostudies-arrayexpress

RNA-seq analysis of the effect of BSA and NaOH added to standard culturing medium on THP-1 macrophages

Project description:The data is supplementary to the RNA-seq analysis of LPS and palmitate stimulation of THP-1 macrophages (E-MTAB-6064), where palmitate for the cell treatment was dissolved in sodium hydroxide and coupled with BSA at a molar ratio 7.5:1. Here we stimulated THP-1 macrophages with the corresponding concentration of BSA (4%) and NaOH (0.4 mM) in the presence of 10 nM phorbol 12-myristate 13-acetate (PMA) for 24 hours added to the standard RPMI 1640 medium with 10% fetal bovine serum (FBS) to estimate the effects and compared them with unstimulated THP-1 macrophages cultured in RPMI 1640 medium with 10% FBS and 10nM PMA.

2019-05-17 | E-MTAB-6439 | biostudies-arrayexpress

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