ABSTRACT: Aryl Hydrocarbon Receptor (AHR) gene expression altered by 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) but inhibited by GNF-351 (GNF), a potent AHR antagonist
Project description:The aryl hydrocarbon receptor (AHR) mediates the toxic effects of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Frogs are very insensitive to the toxic effects of TCDD.
Project description:We report mRNA sequencing from decidual stromal cells after 24 hours and 6 days treatment with Aryl Hydrocarbon Receptor (AHR) activators 100 µM L-kynurenine or 10 nM TCDD (2,3,7,8-Tetrachlorodibenzo-p-dioxin)
Project description:The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that mediates the toxic effects of the environmental contaminant, dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD). Dioxin causes a diverse range of toxic responses, including hepatic damage and lethal wasting syndrome; however, the mechanisms of dioxin-induced toxicity are still unknown. Here we show that the loss of TCDD-inducible poly(ADP-ribose) polymerase (TIPARP; ARTD14), an ADP-ribosyltransferase and AHR repressor, increases sensitivity to dioxin-induced toxicity and lethality. Tiparp-/- mice treated with a single injection of 100 mg/kg dioxin display an accelerated lethal wasting syndrome with no Tiparp-/- mice surviving beyond day 5; all Tiparp+/+ mice survived up to 30 days post treatment. Tiparp-/- mice displayed dramatic increases in liver steatosis and hepatotoxicity. At the molecular level, TIPARP selectively ADP-ribosylates AHR, but not AHR nuclear translocator (ARNT) and the Tiparp-dependent repression of AHR is reversed by the ADP-ribosylase and macrodomain containing protein MacroD1, but not MacroD2. These results describe previously unidentified roles for Tiparp, MacroD1, and ADP-ribosylation in AHR signaling, dioxin toxicity and lethality. 12 samples were analyzed. There were 4 treatment groups and each treatment group was done in triplicate. Gene expression changes were determine in hepatic RNA isolated from (1) corn oil treated C57BL/6;129Sv mice; (2) 30 ug/kg/bw 2,3,7,8-Tetrachlorodibenzo-p-dioxin C57BL/6;129Sv mice; (3) corn oil treated C57BL/6;129Sv Tiparp-/- mice; and (4) 30 ug/kg/bw 2,3,7,8-Tetrachlorodibenzo-p-dioxin C57BL/6;129Sv Tiparp-/- mice
Project description:Aryl hydrocarbon receptor ChIP-Seq performed in livers of female mice gavaged with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 2hrs
Project description:Aryl hydrocarbon receptor ChIP-Seq performed in livers of male mice gavaged with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 2hrs
Project description:The aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters differentiation of B cells and suppresses antibody production. The objectives of this study was to use a combination of whole genome, microarray-based chromatin immunoprecipitation (ChIP-on-chip) and time course gene expression microarray analysis on the mouse B-cell line CH12.LX following exposure to lipopolysaccharide (LPS) or LPS and TCDD to identify the primary and downstream transcriptional elements of B-cell differentiation that are altered by the AHR.
Project description:Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of various environmental contaminants, like polycyclic and halogenated aromatic hydrocarbons, including the most potent agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation. The purpose of this study was to investigate the temporal pattern of AHR expression during directed differentiation of human embryonic stem cells (hESC) into neural progenitor, early mesoderm and definitive endoderm cells. Additionally, we studied the effect of AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression profile in hESCs and differentiated cells by RNA-seq, accompanied by identification of AHR binding sites by ChIP-seq and epigenetic landscape analysis by ATAC-seq. . We show that AHR is differentially regulated in distinct lineages, provide evidence that TCDD impairs differentiation of hESCs and identify novel potential AHR target genes which expand our understanding on the role of this protein in different cell types.
Project description:Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of various environmental contaminants, like polycyclic and halogenated aromatic hydrocarbons, including the most potent agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation. The purpose of this study was to investigate the temporal pattern of AHR expression during directed differentiation of human embryonic stem cells (hESC) into neural progenitor, early mesoderm and definitive endoderm cells. Additionally, we studied the effect of AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression profile in hESCs and differentiated cells by RNA-seq, accompanied by identification of AHR binding sites by ChIP-seq and epigenetic landscape analysis by ATAC-seq. . We show that AHR is differentially regulated in distinct lineages, provide evidence that TCDD impairs differentiation of hESCs and identify novel potential AHR target genes which expand our understanding on the role of this protein in different cell types.
Project description:Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of various environmental contaminants, like polycyclic and halogenated aromatic hydrocarbons, including the most potent agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation. The purpose of this study was to investigate the temporal pattern of AHR expression during directed differentiation of human embryonic stem cells (hESC) into neural progenitor, early mesoderm and definitive endoderm cells. Additionally, we studied the effect of AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression profile in hESCs and differentiated cells by RNA-seq, accompanied by identification of AHR binding sites by ChIP-seq and epigenetic landscape analysis by ATAC-seq. . We show that AHR is differentially regulated in distinct lineages, provide evidence that TCDD impairs differentiation of hESCs and identify novel potential AHR target genes which expand our understanding on the role of this protein in different cell types.
Project description:The aryl hydrocarbon receptor (AHR) mediates the toxic effects of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Frogs are very insensitive to the toxic effects of TCDD. Experiment Overall Design: XLK-WG cells (ATCC) were grown to ~90% confluence in RPMI-1640 media supplemented with 20% FBS at 29 degrees and 5% CO2. Cells were subsequently exposed to 100 nM TCDD, FICZ, or DMSO vehicle (0.25%) for 3 hr prior to extraction of total RNA. Experiment Overall Design: Study included three complete biological replicates of each treatment.
