Project description:TCDD is an environmental contaminant that elicits a number of hepatic effects including fat accumulation, inflammation, and fibrosis that can progress to hepatocellular carcinoma. RNA-Seq and targeted metabolomics were integrated with complementary dioxin response element (DRE) location and aryl hydrocarbon receptor (AhR) ChIP-Seq data to further investigate the hepatotoxicity of TCDD. Our integrative analysis identified changes similar to the Warburg effect observed in cancer cells, including pyruvate kinase isoform switching (PKM1 to PKM2), and an increase in the glutaminase (GLS1) GAC:KGA isoform ratio. Consequently, metabolites are redirected towards the pentose phosphate pathway, serine biosynthesis, and glutaminolysis. We propose that the effects of TCDD on central carbon and amino acid metabolism represents AhR-mediated hepatic metabolic reprogramming in order to increase NADPH production as an oxidative stress counter-measure.
Project description:We report sequencing of chromatin immunoprecipitated DNA (ChIP-Seq) of Aryl Hydrocarbon Receptor (AHR) targets from decidual stromal cells with kynurenine treatment and normal decidualization media
Project description:Emerging studies revealed an immunomodulatory role of the Aryl hydrocarbon receptor (AhR), a receptor sensing environmental contaminants, and involved in their detoxification. Besides its function as a transcription factor, AhR can participate in non-genomic signaling through ubiquitination and phosphorylation-dependent processes. In this study, a multi-PTM-omics approach, including proteome, ubiquitome, and phosphoproteome, was utilized to examine mechanisms of non-genomic AhR-signaling in endotoxin-activated monocyte-derived macrophages. This dataset entails proteome and phosphoproteome data.
Project description:The aryl hydrocarbon receptor repressor (AHRR) is a bHLH-PAS protein closely related to the aryl hydrocarbon receptor (AHR). AHRR is a transcriptional repressor of AHR and hypoxia-inducible factor (HIF) and is regulated by an AHR-dependent mechanism. Zebrafish possess two AHRR paralogs; AHRRa regulates constitutive AHR signaling during development, while AHRRb regulates polyaromatic hydrocarbon-induced gene expression. However, very little is known about the endogenous roles of AHRRs in development and physiology. The objective of this study was to elucidate the role of AHRRs during zebrafish development using a loss-of-function approach followed by microarray analysis. Zebrafish embryos were microinjected with morpholino oligonucleotides (MO) against AHRRa or AHRRb to disrupt endogenous signaling during development. At 72 hours post-fertilization (hpf), embryos were sampled for microarray analysis. Agilent microarray analysis revealed altered expression of 279 and 116 genes with knockdown of AHRRa and AHRRb, respectively. In AHRRa-morphant embryos, 97 genes were up-regulated and 182 genes were down-regulated. Among the differentially expressed genes were a large number related to photoreceptor development, including cone-specific genes such as short-wave, medium-wave and long-wave sensitive opsins (opn1sw1, opn1sw2, opn1mw1, opn1lw2), phosphodiesterases (pde6H, pde6C), retinol binding protein (rbp4l), phosducin, and arrestin. These results suggest that AHRRa may be involved in photoreceptor development. In addition, AHRRa knockdown also caused up-regulation of embryonic hemoglobin (hbbe3), suggesting a role for AHRR in regulating hematopoiesis. Knockdown of AHRRb caused up-regulation of 31 genes and down-regulation of 85 genes, without enrichment of genes related to any specific biological process. Overall, these results suggest that AHRRs play multiple roles during development. Three different treatment conditions (Control-MO, AHRRa-MO and AHRRb-MO) and two replicates per treatment
Project description:Analysis of gene expression in isolated mouse lung dendritic cells isolated during influenza A virus infection, with and without activaiton of the aryl hydrocarbon receptor (AHR).
Project description:We have generated transgenic mice expressing constitutively activated aryl hydrocarbon receptor (CA-AhR) to examine the biological consequences of AhR activation.. We used microarrays to identify genes that are regulated by AhR.
Project description:Aryl hydrocarbon receptor (AhR) is an important ligand-activated transcription factor involved in the regulation of various important physiological functions. AhR can be activated by a variety of signals with different affinities, including xenobiotics and endogenous signals. In the absence of ligand, AhR forms a stable multiprotein complex in the cytosol with the chaperone Hsp90 and co-chaperon p23, XAP2.
Project description:[original Title] Comparison of expression data of primary murine melanocytes from aryl hydrocarbon deficient mice and corresponding wild-type C57BL/6 mice Melanin is produced exclusively by melanocytes and melanogenesis is the vital response to protect skin cells against Ultraviolet B (UVB)-induced DNA damage. The aryl hydrocarbon receptor (AhR) is a transcription factor, which may be involved in the physiological tanning response. Normal murine melanocytes express functional AhR. We tested gene expression in WT versus AhR-deficient mice primary murine melanocytes, isolated from the skin and cultivated for several passages. Skin epidermal cells from 2 individual C57BL/6 mice and 2 individual AhR-deficient mice (deletion of exon2, AhRtm1Bra) were grown for 6-8 weeks in selection medium to propagate melanocytes.
Project description:To identify aryl hydrocarbon receptor (AHR) dependent transcriptional changes in mouse colon stem cells, we performed RNA sequencing of colon organoids from wildtype and AhR deficient mice stimulated with an high affinity AHR ligand, 5nM FICZ for 4 hours.
