LXRα genomic binding in murine macrophages
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1151146 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30346541.fastq.gz | Fastqsanger.gz | |||
| SRR30346542.fastq.gz | Fastqsanger.gz |
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Project description:Liver X receptors (LXRα and LXRβ) are nuclear receptor transcription factors that play crucial roles in regulating metabolic and immune functions in macrophages. Both receptors are present in macrophages and exhibit significant sequence similarity, yet their specific roles in various macrophage models, especially in inflammatory contexts, remain underexplored. Prior research has demonstrated that ligand-activated LXRs can suppress the expression of pro-inflammatory cytokines in macrophages. Here, we explored the genomic landscape of LXRa under inflammatory conditions using BMDM lacking LXRb as previously described (de la Rosa et al 2024); we treated BMDM with synthetic LXR ligand GW3965 alone or in combination with lipopolysaccharide for 24h.
2024-08-27 | GSE275506 | GEO
Project description:The LXR proteins, LXRα and LXRβ, are transcription factors that belong to the nuclear receptor superfamily. LXRs are activated by oxysterols and control the transcription of genes involved in the regulation of cholesterol and fatty acid metabolism. They also mediate several aspects of macrophage biology, including inflammatory responses, cell survival in response to infection and phagocytosis of apoptotic cells. LXRs share a high degree of sequence homology and most of their functions are believed to be performed similarly by LXRα and LXRβ. However, the individual, transcriptional roles of each LXR isoform have not been characterized in detail, in part due to the lack of specific experimental tools that can discriminate between LXRα and LXRβ actions. To identify common and differential transcriptional functions of LXR nuclear receptors in macrophages, we developed a cellular model of stable expression of FLAG-tagged LXRα or LXRβ in LXR-null immortalized murine bone marrow-derived macrophages (parental line published Elife. 2015 Jul 14;4:e08009. doi: 10.7554/eLife.08009). To take a deeper insight into the epigenomic features of LXR nuclear receptors, we performed chromatin immunoprecipitation coupled to next-generation sequencing (ChIP-seq) to identify genome-wide binding locations of LXRα and LXRβ in the presence of a synthetic agonist (GW3965, 1uM). Additionally, we identified genome-wide DNA locations of acetylation mark on lysine 27 of histone H3 (H3K27ac), upon LXR agonist (GW3965, 1uM) and antagonist (GW2033, 1uM) treatment. Collectively, these studies will increase our understanding of common and differential genomic actions of LXRα and LXRβ in cultured murine macrophages.
2017-10-19 | GSE104027 | GEO
Project description:The Liver X receptors (LXRα and LXRβ) are members of the nuclear receptor superfamily of transcription factors, and play key roles in the coordination of both metabolic and immune responses in macrophages. Both LXRs are expressed in macrophages and they share a high degree of sequence homology but their individual roles in different models of macrophage cultures, particularly in response to inflammation, have not been characterized. Previous studies have shown that ligand pre-treated LXRs repress the induction of pro-inflammatory cytokines in macrophages. Here, we show evidence that the expression of LXRα (but not LXRβ) is transcriptionally regulated at late phases of an LPS-induced inflammatory response in bone marrow-derived macrophages (BMDMs). Regulation of LXRα expression is controlled at the transcriptional levels by inflammatory signaling networks. Transcriptional profiling studies and ChIP-seq data identified a number of innate immune pathways whose expression is substantially controlled by LXRα in BMDMs. In summary, our data shows that LXRα plays a previously unrecognized role in innate immunity by transcriptional regulation of a battery of inflammatory genes through TLR and Type-I IFN-dependent signaling in macrophages.
2020-05-01 | GSE130586 | GEO
Project description:The Liver X receptors (LXRα and LXRβ) are members of the nuclear receptor superfamily of transcription factors, and play key roles in the coordination of both metabolic and immune responses in macrophages. Both LXRs are expressed in macrophages and they share a high degree of sequence homology but their individual roles in different models of macrophage cultures, particularly in response to inflammation, have not been characterized. Previous studies have shown that ligand pre-treated LXRs repress the induction of pro-inflammatory cytokines in macrophages. Here, we show evidence that the expression of LXRα (but not LXRβ) is transcriptionally regulated at late phases of an LPS-induced inflammatory response in bone marrow-derived macrophages (BMDMs). Regulation of LXRα expression is controlled at the transcriptional levels by inflammatory signaling networks. Transcriptional profiling studies and ChIP-seq data identified a number of innate immune pathways whose expression is substantially controlled by LXRα in BMDMs. In summary, our data shows that LXRα plays a previously unrecognized role in innate immunity by transcriptional regulation of a battery of inflammatory genes through TLR and Type-I IFN-dependent signaling in macrophages.
2022-12-31 | GSE200922 | GEO
Project description:The Liver X receptors (LXRα and LXRβ) are members of the nuclear receptor superfamily of transcription factors, and play key roles in the coordination of both metabolic and immune responses in macrophages. Both LXRs are expressed in macrophages and they share a high degree of sequence homology but their individual roles in different models of macrophage cultures, particularly in response to inflammation, have not been characterized. Previous studies have shown that ligand pre-treated LXRs repress the induction of pro-inflammatory cytokines in macrophages. Here, we show evidence that the expression of LXRα (but not LXRβ) is transcriptionally regulated at late phases of an LPS-induced inflammatory response in bone marrow-derived macrophages (BMDMs). Regulation of LXRα expression is controlled at the transcriptional levels by inflammatory signaling networks. Transcriptional profiling studies and ChIP-seq data identified a number of innate immune pathways whose expression is substantially controlled by LXRα in BMDMs. In summary, our data shows that LXRα plays a previously unrecognized role in innate immunity by transcriptional regulation of a battery of inflammatory genes through TLR and Type-I IFN-dependent signaling in macrophages.
2024-04-02 | GSE254257 | GEO
Project description:OBJECTIVE: The liver X receptor α (LXRα) is a ligand-dependent nuclear receptor and the major regulator of reverse cholesterol transport in macrophages. This makes it an interesting target for mechanistic study and treatment of atherosclerosis. METHODS AND RESULTS: We optimized a promising stilbenoid structure (STX4) in order to reach nanomolar effective concentrations in LXRα reporter-gene assays. STX4 displayed the unique property to activate LXRα effectively but not its subtype LXRβ. The potential of STX4 to increase transcriptional activity as an LXRα ligand was tested with gene expression analyses in THP1-derived human macrophages and oxLDL-loaded human foam cells. Only in foam cells but not in macrophage cells STX4 treatment showed athero-protective effects with similar potency as the synthetic LXR ligand T0901317 (T09). Surprisingly, combinatorial treatment with STX4 and T09 resulted in an additive effect on reporter-gene activation and target gene expression. In physiological tests the cellular content of total and esterified cholesterol was significantly reduced by STX4 without the undesirable increase in triglyceride levels as observed for T09. CONCLUSIONS: STX4 is a new LXRα-ligand to study transcriptional regulation of anti-atherogenic processes in cell or ex vivo models, and provides a promising lead structure for pharmaceutical development.
2013-09-05 | GSE39079 | GEO
Project description:As a cholesterol sensor, nuclear receptor liver X receptor (Lxr) activated by oxysterols is an important factor regulating cholesterol homeostasis and plays central roles in the transcriptional control of cholesterol metabolism. Lxrα is one of the liver X receptor(Lxrs) subtypes. Lxrα is abundantly expressed in liver, small intestine, adipose, kidney, adrenal tissues, and macrophages. Lxrα's regulation of lipid metabolism is well known but its regulation of other downstream genes remains unclear.In order to investigate the regulating effect of Lxrα on other genes, we used the second-generation transcriptome sequencing(RNA-seq) to determine the expression changes of each gene in Lxrα-/- mices comparing with wild type mices.
2024-10-30 | GSE161880 | GEO
Project description:Post-transcriptional gene regulation by miRNAs and RNA binding proteins (RBP) is important in development, physiology and disease. To examine the interplay between miRNAs and the RBP ELAVL1 (a.k.a. HuR), we mapped miRNA binding sites on a transcriptome-wide scale in WT and Elavl1 knockout murine bone marrow-derived macrophages. Proximity of ELAVL1 binding sites attenuated miRNA binding to transcripts and promoted gene expression. Transcripts that regulate angiogenesis and macrophage/ endothelial cross talk were preferentially targeted by miRNAs, suggesting that ELAVL1 promotes angiogenesis, at least in part, by antagonism of miRNA function. We found that ELAVL1 antagonized binding of miR-27 to the 3’UTR of Zfp36 mRNA and alleviated miR-27-mediated suppression of the RBP ZFP36 (a.k.a. Tristetraprolin). Thus the miR-27-regulated mechanism synchronizes the expression of ELAVL1 and ZFP36. This study provides a resource for systems-level interrogation of post-transcriptional gene regulation in macrophages, a key cell type in inflammation, angiogenesis and tissue homeostasis. Bone marrow derived macrpohges mRNA profiles of 7-day cultured wild type (WT) and Elavl1l-/- mouse bone marrow cells were generated by deep sequencing, with 4 biologic duplication, using Illumina GAII.
2015-04-23 | E-GEOD-63199 | biostudies-arrayexpress
Project description:TLR-dependent transcriptional reprogramming of LXRα cistrome in bone marrow-derived macrophages
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Project description:TLR-dependent transcriptional reprogramming of LXRα cistrome in bone marrow-derived macrophages
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