Similar Datasets
Project description:We profiled RXRα binding to genomic loci in peritoneal macrophages using ChIPmentation.
2024-12-16 | GSE254407 | GEO
Project description:To examine more closely the varied effects of RA receptor deletions on peritoneal MFs, and determine whether inactivation of RXRα and RARγ elicited superimposable effects on different LPM clusters (as predicted if they operate as a heterodimer, a known propensity of RXR proteins), we performed single-cell RNA sequencing (scRNAseq) analyses on total CD11b+CD115+ peritoneal cells from BMC mice edited for several RA receptors, 17 days after reconstitution.
2024-12-16 | GSE254572 | GEO
Project description:We profiled the transcriptional effects of NR deficiencies on peritoneal macrophages.
2024-12-16 | GSE254406 | GEO
Project description:We performed RNAseq profiling of sorted LYVE1+CD206+ MFs from WT, RARγ mutant and RXRα mutant converting macrophages (Conv.MF).
2024-12-16 | GSE273340 | GEO
Project description:Nuclear receptors undergo ligand-dependent conformational changes that are required for corepressor-coactivator exchange, but whether there is an actual requirement for specific epigenetic landmarks to impose ligand dependency for gene activation remains unknown. Here we report an unexpected and general strategy that is based on the requirement for specific cohorts of inhibitory histone methyltransferases (HMTs) to impose gene-specific gatekeeper functions that prevent unliganded nuclear receptors and other classes of regulated transcription factors from binding to their target gene promoters and causing constitutive gene activation in the absence of stimulating signals. This strategy, based at least in part on an HMT-dependent inhibitory histone code, imposes a requirement for specific histone demethylases, including LSD1, to permit ligand- and signal-dependent activation of regulated gene expression. These events link an inhibitory methylation component of the histone code to a broadly used strategy that circumvents pathological constitutive gene induction by physiologically regulated transcription factors.
| S-EPMC1994663 | biostudies-literature
Project description:Nuclear receptors are transcription factors that require multiple protein-protein interactions to regulate target gene expression. We have cloned a 27-kDa protein, termed NIX1 (neuronal interacting factor X 1), that directly binds nuclear receptors in vitro and in vivo. Protein-protein interaction between NIX1 and ligand-activated or constitutive active nuclear receptors, including retinoid-related orphan receptor beta (RORbeta) (NR1F2), strictly depends on the conserved receptor C-terminal activation function 2 (AF2-D). NIX1 selectively binds retinoic acid receptor (RAR) (NR1A) and thyroid hormone receptor (TR) (NR1B) in a ligand-dependent manner, but does not interact with retinoid X receptor (RXR) (NR2B) or steroid hormone receptors. Interestingly, NIX1 down-regulates transcriptional activation by binding to ligand-bound nuclear receptors. A 39-aa domain within NIX1 was found to be necessary and sufficient for protein-protein interactions with nuclear receptors. Northern blot analysis demonstrates low-abundance RNA messages only in brain and neuronal cells. In situ hybridization and immunohistochemistry revealed that NIX1 expression is restricted to the central nervous system and could be confined to neurons in the dentate gyrus of the hippocampus, the amygdala, thalamic, and hypothalamic regions. In summary, protein-protein interactions between the neuronal protein NIX1 and ligand-activated nuclear receptors are both specific and selective. By suppressing receptor-mediated transcription, NIX1 implements coregulation of nuclear receptor functions in brain.
| S-EPMC16516 | biostudies-literature
Project description:Apolipoprotein M (apoM) plays an important role in the biogenesis and the metabolism of anti-atherogenic HDL particles in plasma and is expressed primarily in the liver and the kidney. We investigated the role of hormone nuclear receptors in apoM gene regulation in hepatic cells. Overexpression via adenovirus-mediated gene transfer and siRNA-mediated gene silencing established that hepatocyte nuclear factor 4 (HNF-4) is an important regulator of apoM gene transcription in hepatic cells. apoM promoter deletion analysis combined with DNA affinity precipitation and chromatin immunoprecipitation assays revealed that HNF-4 binds to a hormone-response element (HRE) in the proximal apoM promoter (nucleotides -33 to -21). Mutagenesis of this HRE decreased basal hepatic apoM promoter activity to 10% of control and abolished the HNF4-mediated transactivation of the apoM promoter. In addition to HNF-4, homodimers of retinoid X receptor and heterodimers of retinoid X receptor with receptors for retinoic acid, thyroid hormone, fibrates (peroxisome proliferator-activated receptor), and oxysterols (liver X receptor) were shown to bind with different affinities to the proximal HRE in vitro and in vivo. Ligands of these receptors strongly induced human apoM gene transcription and apoM promoter activity in HepG2 cells, whereas mutations in the proximal HRE abolished this induction. These findings provide novel insights into the role of apoM in the regulation of HDL by steroid hormones and into the development of novel HDL-based therapies for diseases such as diabetes, obesity, metabolic syndrome, and coronary artery disease that affect a large proportion of the population in Western countries.
| S-EPMC2945566 | biostudies-literature
Project description:Nuclear receptors are important bridges between lipid signaling molecules and transcription responses. Beside their role in several developmental and physiological processes, many of these receptors have been shown to regulate and determine the fate of immune cells, and the outcome of immune responses under physiological and pathological conditions. While NLRP3 inflammasome is assumed as key regulator for innate and adaptive immune responses, and has been associated with various pathological events, the precise impact of the nuclear receptors on the function of inflammasome is hardly investigated. A wide variety of factors and conditions have been identified as modulators of NLRP3 inflammasome activation, and at the same time, many of the nuclear receptors are known to regulate, and interact with these factors, including cellular metabolism and various signaling pathways. Nuclear receptors are in the focus of many researches, as these receptors are easy to manipulate by lipid soluble molecules. Importantly, nuclear receptors mediate regulatory mechanisms at multiple levels: not only at transcription level, but also in the cytosol via non-genomic effects. Their importance is also reflected by the numerous approved drugs that have been developed in the past decade to specifically target nuclear receptors subtypes. Researches aiming to delineate mechanisms that regulate NLRP3 inflammasome activation draw a wide range of attention due to their unquestionable importance in infectious and sterile inflammatory conditions. In this review, we provide an overview of current reports and knowledge about NLRP3 inflammasome regulation from the perspective of nuclear receptors, in order to bring new insight to the potentially therapeutic aspect in targeting NLRP3 inflammasome and NLRP3 inflammasome-associated diseases.
| S-EPMC7952630 | biostudies-literature
Project description:Bioluminescent resonance energy transfer (BRET2) is a recently developed technology for the measurement of protein-protein interactions in a live, cell-based system. BRET2 is characterized by the efficient transfer of excited energy between a bioluminescent donor molecule (Renilla luciferase) and a fluorescent acceptor molecule (a mutant of Green Fluorescent Protein (GFP2). The BRET2 assay offers advantages over fluorescence resonance energy transfer (FRET) because it does not require an external light source thereby eliminating problems of photobleaching and autoflourescence. The absence of contamination by light results in low background that permits detection of very small changes in the BRET2 signal. BRET2 is dependent on the orientation and distance between two fusion proteins and therefore requires extensive preliminary standardization experiments to conclude a positive BRET2 signal independent of variations in protein titrations and arrangement in tertiary structures. Estrogen receptor (ER) signaling is modulated by steroid receptor coactivator 1 (SRC-1). To establish BRET2 in a ligand inducible system we used SRC-1 as the donor moiety and ER as the acceptor moiety. Expression and functionality of the fusion proteins were assessed by transient transfection in HEK-293 cells followed by Western blot analysis and measurement of ER-dependent reporter gene activity. These preliminary determinations are required prior to measuring nuclear receptor protein-protein interactions by BRET2. This article describes in detail the BRET2 methodology for measuring interaction between full-length ER and coregulator proteins in real-time, in an in vivo environment.
| S-EPMC1555634 | biostudies-literature
Project description:The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β. Crispr/Cas9-mediated knockout of caspase b, which acts by proteolytic processing of il1β, results in increased bacterial burden and less infiltration of macrophages to sites of mycobacterial infection, thus impairing granuloma development. We also show that a number of immediate early response genes (IEGs) are responsible for orchestrating the initial neutrophil response to mycobacterial infection. Further perturbation of the IEGs exposes egr3 as a key transcriptional regulator controlling il1β transcription.
| S-EPMC5529371 | biostudies-literature