Ahr target genes. The AhR/ARNT heterodimer directly binds .

Ahr target genes The AHRR is an AHR gene target and its expression is up-regulated by AHR signalling. Oct 4, 2024 · ChIP sequencing (ChIP-seq) analysis was performed to identify direct AhR target genes in BMDMs. Using the prototype AhR agonist TCDD, we identified the lectin receptor Cd209a (DC-SIGN) and chemokine Ccl17 as novel AhR target genes. Schematic representation of the integrative approach. 18 On the cellular level, AhR modulates the maturation and function of dendritic cells (DCs), controls the generation and function of regulatory T cells Nov 24, 2014 · AHR has been shown to bind to RELB as well, and this complex can interact with a unique response element within the promoter of a number of RELB target genes 101,103. All animals were killed by decapitation 16 hr after the last dose, and the blood and livers were quickly removed. suppression of hepatic gluconeogenesis. Interestingly, parkin is an AhR target gene, induced by AhR activation in the ventral midbrain of mice, which in turn promotes the degradation of alpha-synuclein . Aug 17, 2012 · The aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) activated complex regulates genes in response to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Jan 13, 2021 · In thyroid-tumor samples, the AhR target genes CYP1A1 and CYP1B1 were upregulated relative to associated healthy tissue and again Kyn stimulation of thyroid-cancer cell lines promoted the acquisition of an EMT program (decreased E-cadherin, and increased SLUG, N-cadherin, and fibronectin levels). , a high or a low isoform 1:3 ratio), which mirrored that of CYP1A1 and AHRR expression. Sep 25, 2024 · CYP1B1 is profibrogenic because inhibition of CYP1B1 attenuated HSC activation and liver fibrosis. Dec 29, 2018 · To study the regulatory mechanism of the Aryl hydrocarbon receptor (AHR), target genes of transcription are necessary for understanding the normal developmental and pathological processes. Sep 5, 2019 · The aryl hydrocarbon receptor (AhR) is a well-known ligand-activated cytoplasmic transcription factor that contributes to cellular responses against environmental toxins and carcinogens. Jan 28, 2022 · Hence, AHR and NRF2 regulate and share a subset of common target genes with antioxidant properties, suggesting that AHR may be an essential regulator of the redox status of the cell. rrrc. I3P did not only induce AHR nuclear translocation and transcription, but enhanced the motility of GBM May 23, 2022 · The induction of target genes by the human AhR could be observed after long periods of treatment (24 h after treatment with 3-methycholanthrene, 3MC) . Feb 1, 2014 · These genes are members of the [ah] gene battery, AhR-Nrf2 gene battery and other genes that have been shown to be TCDD regulated in multiple species (Boutros et al. , 2008, Forgacs et al. AhR repressor (AhRR) is another of the key target genes activated in the AhR Jun 1, 2024 · However, NQO1 expression is also regulated by the aryl hydrocarbon receptor (AhR) and cannot be upregulated in response to certain chemical inducers in the liver of transgenic AhR knockout mice [40, 41]. , 2006, Yeager et al. The AhR/ARNT heterodimer directly binds Feb 1, 2023 · The probably best examined target genes of the AHR/ARNT complex encode for cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, xenobiotic-metabolizing enzymes that oxidize the invading (AHR-activating) chemical to enhance its polarity and enable its detoxification via the conjugating enzyme system. After the active heterodimer has performed its function, the AHR dissociates from ARNT, is exported Mar 10, 2021 · Aryl hydrocarbon receptor (AHR) was considered to be an important pan-tumor therapeutic target, but small molecule inhibitors targeting AHR target gene IDO1 have failed in clinical trials. Indeed, the product of the prototypic AHR target gene CYP1A1 was identified as the main regulator of AHR-mediated lipid biogenesis . AhR-KO and wild type (WT) male and Dec 3, 2018 · The aryl hydrocarbon receptor (AHR) is a nuclear receptor that modulates the response to environmental stimuli. 5H,I). To further determine the role of SPHK2 in AHR signaling, the SPHK2 inhibitor ABC294640 was utilized. TCDD can cause birth defects, cancer, hepatotoxicity, immunological deficiencies, or death (Schmidt and Bradfield, 1996) . SPHK2 was found enriched on the CYP1A1 promoter, underscoring its role in AHR target gene activation. The E3 ligase parkin directs the ubiquitination of proteins such as alpha-synuclein, Cdc- Rel, synphilin-1, and plays an important role in the progression of PD. , 2000, Tijet et al. These regulators include transcription-factors such as NF-κB [ 268 ], AP-1 [ 269 ], β-catenin [ 270 ], proliferator-activated receptor γ (PPARγ) [ 271 ] and the master regulator Gene target information for AHR - aryl hydrocarbon receptor (human). Studies in knockout and transgenic mice indicate that the AHR plays a vital role in the development of liver and regulation of reproductive, cardiovascular, hematopoieti … Feb 28, 2008 · To determine the exact induction of AhR target genes, we used 3MC as an AhR activator. Importantly, the expression of all 12 AHR target genes was increased compared with the control group, consistent with the role of AHR agonists functioning as transcriptional activators (supplemental Figure 12). To stimulate studies on responsible action mechanisms the commentary is focused on human AHR target genes and crosstalk with transcription factors. 4e). Nov 16, 2021 · However, 97 genes were differentially expressed at D14, and further analysis revealed that 12 of 97 were AHR target genes (Figure 6A-B). It was recognized historically for its role in toxicology but, in recent decades, it has been increasingly recognized as an important modulator of disease—especially for its role in modulating immune and inflammatory responses. Nov 11, 2023 · In the nucleus, AHR releases its chaperons 21 and builds a stable dimer with the AHR nuclear translocator (ARNT) 22, 23. The coordinated interaction between Sp1 and AhR was identified to be DNA mediated. This study demonstrates for the first time an increase in the expression of the aryl hydrocarboxylic receptor gene and its . 8d Activation of AHR with TCDD (Fig. Jan 28, 2022 · The aryl hydrocarbon receptor (AHR) is a cytoplasmic transcription factor that is well-known for regulating xenobiotic metabolism. To develop a comprehensive view of the AHR target network, we analyzed gene expression and DNA binding data under a variety of gene–environment combinations, including wild-type cells and cells with a DNA-binding–deficient mutant AHR, in naive cells and in cells exposed to two different ligands, BaP and TCDD. However, recent studies have highlighted that xenobiotic receptors also play a key role in the regulation of lipid metabolism and therefore function also as metabolic sensors. AHR has been implicated in many diseases that are Feb 24, 2023 · In the nucleus, the AHR binds with the ARNT and forms an active heterodimer, which modulates the expression of target genes by binding to xenobiotic responsive elements (XRE, 5’-CGCGTG-3'), thus recruiting coactivators including NCoA-2 and p/CIP and transactivating a variety of genres including the hydroxylases CYP1A1 and CYP1B1, which Apr 11, 2024 · Endogenous AhR ligands, such as Kynurenine (Kyn) and arachidonic acid, induce the translocation of AhR from the cytoplasmic matrix to the nucleus, thereby regulating the transcription of various target genes . elegans SKN-1 induces several components of the UPR target genes, including XBP1 and ATF6, which induce a UPR program for maintaining ER integrity and protein homeostasis , although the induction of its UPR target genes may be through NRF1 . 666 target genes of the AHR transcription factor in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. 1. introns 2 and 3; that we called A, B, C and D cis-regulatory elements hereafter) and the binding is enhanced Mar 25, 2023 · Furthermore, AhR-deficient microglia showed impaired clearance of myelin debris and defected phagocytic capacity. 30, 31 To determine whether STING1 promotes CYP-related xenobiotic metabolism in an AHR-dependent fashion, we assessed the induction of the representative AHR-target genes CYP1A1 and IL22 in response to classical tryptophan-derived AHR May 17, 2016 · To induce gene expression of classical AhR target genes, the ligand bound AhR translocates into the nucleus, interacts with AhR-nuclear translocator (ARNT) and binds to xenobiotic response Jul 1, 2023 · Following the dimerization of nuclear AhR with an AhR nuclear translocator (ARNT), the AhR-ARNT heterodimer binds to the promoters of AhR-target genes and triggers gene transcription. of AHR target genes while PP and HPP did not influence their levels in multiple cell types. Jan 31, 2024 · This leads to induction of target genes, such as cytochrome P450 family 1 subfamily A (CYP1A), in order to promote the elimination of the AhR ligand. The AHR target gene AHR repressor (AHRR) inhibits AHR signaling through mechanisms including competition for ARNT- and XRE-binding, closing of In addition to forming heterodimers with many other bHLH-PAS proteins, including the aryl hydrocarbon receptor (AhR) and hypoxia-inducible factors 1alpha, 2alpha and 3alpha, Arnt can also form homodimers when expressed from its cDNA in vitro or in vivo. 4. Dec 10, 2010 · Whereas the mechanism for AHR induction of target genes is well understood, it is not known how AHR activation produces any TCDD toxicity. In addition, TCDD treatment was capable of enhancing protein translation (Fig. relative to associated healthy tissue [15] and again Kyn stimulation of thyroid-cancer cell. Genome-wide association studies and candidate gene studies have identified SNPs near AHR target genes that are significantly associated with AHR-regulated phenotypes, such as cigarette smoking (AHRR) , psoriasis (CYP1A1) , warfarin response (CYP1A1) , hepatocellular carcinoma (CYP1A1) , atherosclerosis (CYP1A1 and AHRR) [57,58,67,68,69], coffee Genes. In this study, we used RNA-sequencing to identify the signature of the AHR target genes regulate … Transient AHR modulation is often necessary for physiologic functions whereas TCDD-mediated sustained receptor activation has been demonstrated to be responsible for toxic outcomes. Apr 7, 2018 · Aryl hydrocarbon receptor (AhR) is widely expressed by different cell types throughout the body. Molecules with red circles denote direct AHR target genes that were upregulated, whereas molecules with blue circles denote genes that were downregulated. 5G). Oct 16, 2024 · The aryl hydrocarbon receptor (AHR) is a member of the basic helix–loop–helix (bHLH)/PER–ARNT–SIM superfamily of ligand-dependent transcription factors 1 (Fig. Moreover, the AHR and NRF2 target gene batteries partially overlap, the gene expression of NQO1, GST or UGT1A1, for instance, is under control of both pathways. Oct 27, 2022 · Model for the activation of AHR target genes in the presence of Kyn and TCDD. Furthermore, among the direct AHR target genes, the expression level increases with the number of AHR-binding DRE sites in the proximal promoter regions. AHR has also emerged as a potential therapeutic target for the treatment of human diseases and different cancers, including breast cancer. Along those lines, our studies in adult mice and adult human lung cells indicate that AHR deficiency increases, whereas AHR activation by OM decreases, oxidative Jun 17, 2019 · Among the most upregulated DEGs were bona fide AhR target genes, such as Ahrr and Cyp1a1, as well as Ido1, a gene that is consistently elevated in DCs following AhR stimulation (4, 26, 34, 35). We also tested whether inhibition of hexokinase Mar 15, 2022 · First, AhR target genes exhibited abrogated or augmented regulation after siRNA-mediated suppression of ARNT isoform 3 or isoform 1, respectively (i. 1). Flies of the same genotype developed on the standard nutrient medium were used as a control. , 2009). Signalling by the AHR leads to three biological pathways referred to as the adaptive metabolic pathway, the toxic pathway, and the developmental pathway. We explored the role of AhR in tumor cell lines and patients using genomic data sets and discuss the extent to which AhR can be considered as a therapeutic target. One of the AHR target genes is the AHR repressor (AHRR), whose product competes with the AHR for binding to ARNT . These results suggest that a high or a low ARNT isoform 1:3 ratio corresponds to stunted or enhanced AhR Dec 29, 2018 · The mRNA levels of AHR target genes were measured by RT-PCR in testes of UAS-AhR/Tj-GAL4; ss aSc flies fed with exogenous ligands for 2 days. e. In this review we discuss the role of AhR in the regulation of the immune response in the context of autoimmunity, infection and cancer, as well as the potential opportunities and challenges of developing AhR targeted therapeutics. One is proteasomal degradation of the AHR protein, while the other is negative feedback regulation of AHR activation by the AHR repressor (AHRR) . The Ahr/microRNA-212/132 axis in T cells regulates IL-10 production to maintain intestinal homeostasis. AhR is activated by a range of structurally diverse compounds from the environment, microbiome, natural products, and host metabolism, suggesting that AhR possesses a rather promiscuous ligand binding site In the nucleus, together with its binding partner AHR nuclear translocator (ARNT), AHR can induce transcription of various target genes featuring dioxin-responsive elements (DREs) as AHR-ARNT binding sites [10, 11]. It is encoded by a gene located on chromosomes 7 and 12 in humans 26 and mice, 27 respectively. 2). In MCF-7 cells, AHR binding is detectable in a cluster of cis-regulatory elements in the vicinity of HK2 exon 3 (i. Jan 1, 2020 · Activated AhR forms a complex with hypo-phosphorylated Rb that prevents E2F-dependent transcriptional activation of S-phase target genes leading to cell cycle arrest [23]. Altogether, these results demonstrated that BW723C86 upregulates the expression of AhR target genes in human macrophages in a 5-HT 2B –dependent manner. We observed that CH-223191 limits the induction of CYP1A1, CYP1B1 and ALDH3A1 upon BaP treatment, consistent with AHR involvement (Figure 4E). Silencing the TCDD-activated AHR target genes was sufficient to reduce protein synthesis (Fig. AHR_HUMAN,P35869 We would like to show you a description here but the site won’t allow us. These DNA consensus motifs are recognized as DRE or XRE The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820). We then performed a short-period kinetic experiment using 3MC and confirmed that the modulation of the Firefly luciferase activity caused by AHR-1 occurred after only 24 h of treatment and not Oct 15, 2024 · The aryl hydrocarbon receptor (AhR), a transcription factor activated by various metabolites and xenobiotics, influences how immune cells respond to the cytokines that direct their differentiation and function. cause only an increase in the transcription levels of AHR target genes in mammals . The protein encoded by this gene is a ligand-activated helix-loop-helix transcription factor involved in the regulation of biological responses to planar aromatic Dec 9, 2023 · The AHR-ARNT complex then initiates transcription of target genes harboring xenobiotic-responsive elements (XRE) . AHRR is known to be an AHR-target gene, and AHRR Jan 1, 2022 · The AhR knock out (AhR-KO) rat model was generated using CRISPR/Cas9-mediated disruption of the AhR basic helix loop helix DNA binding domain. Finally, IL4I1 activity toward tryptophan leading to production of AHR-activating products is very low, and should be negligible when tryptophan-degrading enzymes of higher affinity compete for the substrate. Sep 23, 2022 · In this study, we used RNA-sequencing to identify the signature of the AHR target genes regulated by the pollutant 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and the endogenous ligand kynurenine (Kyn Jan 13, 2021 · In thyroid-tumor samples, the AhR target genes CYP1A1 and CYP1B1 were upregulated. Upon ligand binding, AHR undergoes a conformational change, and the AHR/ligand complex is released from chaperone proteins; AHR is subsequently translocated into the nucleus where AHR heterodimerizes with ARNT; AHR/ARNT binds to XREs of target genes, regulating their expression. , 2003) and reports of defects in the Nov 27, 2024 · Clinical resource with information about AHR, An atlas of genetic influences on human blood metabolites. 1,2,3,4 Numerous genes are regulated by AhR, including those that encode xenobiotic metabolizing Apr 11, 2020 · The tryptophan metabolites, which ameliorate intestinal inflammation , may also be derived from the microbiota and activate the AHR target genes on mouse colonocytes (Fig. 4B) . Oct 15, 2022 · The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) regulates cellular detoxification, proliferation and immune evasion in a range of cell types and tissues, including cancer cells. Silencing SPHK2 reduced AHR expression and its target gene CYP1A1, while SPHK2 overexpression enhanced AHR activity. Jan 6, 2021 · In mice and humans, AHR is an 848-amino acid-long protein. The most potent known AHR agonist is 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD). , Human metabolic individuality in biomedical and pharmaceutical Similarly, an NLS-deficient AHR mutant impaired SPHK2 nuclear translocation. Activation of AHR regulates ALDH1A3, ADGRF1, CYP1A1, ABCG2 and SCIN. In the nucleus, AhR dimerizes with its partner protein AhR nuclear translocator (ARNT) and binds to xenobiotic-responsive elements (XREs) in the regulatory region of target genes, inducing their transcription [8, 9]. Therefore, it may be an alternative therapeutic target for treating metabolic disorders such as dyslipidemia ( 58 ). We found significant enrichment of ChIP-seq peaks distributed across the genome, corresponding to 120 unique common genes . , Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption. Finally, posttranslational modifications of the AHR and its interaction partners, epigenetic regulation of AHR and its target genes, as well as AHR-mediated induction of enzymes that degrade AHR-activating ligands may contribute to the context-specificity of AHR activation. Apr 22, 2022 · Abstract Aryl hydrocarbon receptor (AHR) is a highly conserved ligand-dependent transcription factor, whose target genes play a key role in detoxification, regulation of developmental processes, maintenance of eukaryotic homeostasis, and metabolism of medicinal compounds. In addition, both AhR ligand called 3-methylcholanthrene and β Mar 24, 2009 · Given the large enrichment of developmental clusters in the AHR target network, a higher order understanding of the connections among disease state, environment, and AHR target genes will require extending these studies to the diverse tissues of the developing organism and defining a target network map at the level of the whole organism, a task AhR is a direct target gene of miR-29. PCB 153, mediated by AhR, can be considered as a ‘secondary strike’ mechanism for obesity/non-alcoholic fatty liver disease in the context of a HFD ( 59 ). These include proteins such as PD-L1 (programmed cell death 1 ligand, CD274) and PD-1 Nov 30, 2023 · Traditionally, xenobiotic receptors are known for their role in chemical sensing and detoxification, as receptor activation regulates the expression of various key enzymes and receptors. To demonstrate activation of AHR signaling in vivo, transcription of AHR target genes was assessed in male UGSs exposed to TCDD in utero. The AHR/ARNT heterodimer recruits several co-factors 24, binds its Feb 4, 2019 · AHR activation results in its translocation to the nucleus and control of the expression of target genes harbouring AHR-responsive DNA elements (known as dioxin response elements or Oct 5, 2022 · To gain a deeper biological understanding of AHR, we employed genome scale metabolic reconstruction to integrate knockout transcriptomics and metabolomics data, which indicated a role for AHR Oct 1, 2019 · The present commentary is focused on human AHR target genes and associated transcription factors (Table 1) for selected AHR functions (Fig. Instead, the fibrotic induction of Cyp1b1 may have been mediated by the transcriptional factor WT1. We further show the percentage of These AhR-mediated regulations of gene expressions are generally achieved in an AhR-non-canonical signaling pathway manner. 7 ). However, target genes of the Arnt/Arnt homodimer remain to be identified. The classical recognition motif of the AhR/ARNT complex, referred to as either the AhR-, dioxin- or xenobiotic- responsive element (AHRE, DRE or XRE), contains the core sequence 5'-GCGTG-3' [53] within the consensus sequence 5'-T/GNGCGTGA/CG/CA-3' [54] [55] in the promoter region of AhR responsive genes. Jan 28, 2025 · these data suggest a role for AhR in HSC functional regulation, and identify novel HSC AhR target genes that may contribute to the phenotypes observed in AhR-KO mice. Dec 24, 2024 · The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820). Moreover, several AhR ligands, such as resveratrol and quercetin, are compounds proven to extend the lifespan of model AhR target genes include several enzymes involved in the metabolic degradation of ligands, such as CYP1A1, as well as the AhR repressor (AhRR) protein, a negative regulator of AhR signaling. 3 SPHK2 Inhibition or Knockdown Reduces AHR Presence in Nuclear Extracts and Reduces AHR Target Gene Activation. TCDD increased transcription of Cyp1a1, Cyp1b1, and an AHR reporter gene in the UGE and/or UGM . The AhRR protein is similar to the AhR but it cannot bind ligands due to the absence of the PAS B domain in the N-terminal region [18] , [19] . To induce ectopic human <i>AhR</i> gene e … tion of AhR target genes during development (Campbell et al. Unexpectedly, in addition to an increase, we found a decrease and also unchanged expression levels of the Drosophila AHR Gene expression microarray analyses comparing Nfe2l2-null and wild-type MEFs showed that expression of Notch1 and AhR, as well as their target genes, is decreased in Nfe2l2-depleted cells (148, 172). 5F). A pan-tissue … Oct 1, 2023 · The hypoxia inducible factors HIF1A and EPAS1 (endothelial PAS domain protein 1, HIF2α) also bind to ARNT and compete with ligand-bound AHR for the interaction with ARNT, thereby reducing AHR activity. Dec 1, 2018 · One of the key target genes activated in the AhR genomic pathway is the AhR repressor, AhRR [16], [17], [18] (Fig. Nov 17, 2022 · It has shown that BaP, which is a component of cigarette smoke, in addition to the classical AhR target genes (CYP1A, CYP1B), induces expression of the immune checkpoints, which comprise a system of inhibitory mechanisms that regulate autoimmune processes. In this scenario, the modulation depends on specific agonist or antagonist activities of ligands such as indole-3-acetate, indole-3-aldehyde, indole, and tryptamine. We speculate that the AhR pathway can affect the HIF-1α pathway and thus atherosclerosis metabolism, which ultimately regulates the development of The NRF2 homolog in C. Genome-wide association studies have also identified SNPs within genes directly associated with the genomic AhR signaling pathway that might impact AhR binding sites, AhR target gene expression, and inter-individual variability in AhR-dependent toxicity [129,130,131,132]. It is a ubiquitous well Jan 13, 2021 · Its level of expression and activity are specific to each tumor and patient, increasing the difficulty of understanding the activating or inhibiting roles of AhR ligands. Jul 26, 2024 · (A) AhR ligand bound to AhR receptor, will translocate AhR into the nucleus and forms a heterodimer to drive transcription of AhR target genes such as CYP enzymes and regulates the expression of different JAK/STAT-stimulating cytokines including IL-2, IL-10, IL-21, IL-22. In a negative feedback loop limiting AHR activation, degradation of AHR ligands is facilitated by cytochrome P450-dependent Jul 10, 2024 · AHR agonism significantly enriched AHR target genes and CD96 expression and downregulated expression of CXCL13 and other T PH /T FH genes such as ICOS, MAF and IL21 at 48 h (Extended Data Fig. Sep 27, 2016 · Target genes are partially consistent with AHR activated AHRE transcribed genes comprising inter alia ALDH3A1, NQO1 and UGT1A 47. A remarkable increase in the transcription of some AHR target genes was observed (Figure 4). Further investigation of target genes of AhR revealed that spleen tyrosine kinase (SYK) is the downstream effector of AhR and mediated the phagocytic capacity of microglia. Similarly, AhR activation severely compromises the ability of hepatoma cells to progress through G 1 phase due to the induction of p27. Toxic exogenous Oct 1, 2023 · Activation of AhR signaling suppressed HIF-1α-dependent target gene expression; whereas knockdown of AhR significantly increased HIF-1α expression and its target gene expression [133], [134]. After ligand activation, AHR translocates into the nucleus where it dimerizes with ARNT. ABC294640 decreased the expression of the AHR target gene CYP1A1 following TCDF treatment (Figure 2A). , Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. In addition, over 20 single nucleotide polymorphisms in the NQO1 gene have been reported in humans [39]. AHR signalling restrains stemness programmes through transcriptional regulation of factors such as RNF43, an E3 ubiquitin ligase, which counteracts WNT-β The heterodimer then binds to the xenobiotic response element (XRE) and coregulator, modulating the expression of target genes . Nov 11, 2017 · To activate human AHR by exogenous ligands, we used only molecules which are known to act as agonists of this receptor, i. us). Simultaneously, the expression of AhR gene is activated, resulting in the renewal of AhR protein within the cell 7. A well-known target gene is cytochrome P450 Cyp1a1 [ 11 , 13 ]. Hence, AHR and NRF2 regulate and share a subset of common target genes with antioxidant properties, suggesting that AHR may be an essential regulator of the redox status of the cell. Practically, 5’-TNGCGTG-3’ is a DNA consensus motif located in the AhR target gene responsible for the interaction of AhR in the genomic regulatory regions. Notably, transcription factor targets such as AHRR and Nrf2 affect several AHR functions. Here, we examined the effects of human AHR ligands on male fecundity. The cognate sequences for AHR-ARNT are called xenobiotic response elements (XREs), having a core sequence 5′-GCGTG-3′. In addition, a study on Nfe2l2 -null MEFs revealed enhanced IκB kinase β activity, which phosphorylates IκB, the negative regulator of NF-κB Moreover, dendritic cells do not upregulate AHR target genes in relation with IL4I1 expression in vivo. found that activation of the AhR was required for the induction of a subset of transcripts by the cytokine interleukin-4 (IL-4) in human and mouse monocytes. Mar 4, 2021 · This novel role of AHR in lipid biogenesis was also confirmed in non-infected Huh-7 cells and primary human hepatocytes, suggesting that AHR regulates store lipid reserves independently of viral infection. AHR target genes include those encoding cytochrome P450 May 10, 2016 · Moreover, the AhR repressor (AhRR) has been identified as a target gene of AhR, providing a novel mechanism of feedback inhibition of AhR function in that a transcription factor directly induces the expression of its repressor through binding to its cognate regulatory sequence located in the promoter of the target gene. Two AHR regulatory mechanisms have been reported. 1a). , 2013, Nebert et al. The Ahr promoter harbors several The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor, classically associated with the regulation of xenobiotic metabolism in response to environmental toxins. Although this chimeric AhRR/NCOA2 protein has so far only been detected in a small number of soft tissue angiofibromas, it is conceivable that an inactivation of AhRR’s repressive Model for the activation of AHR target genes in the presence of Kyn and TCDD. Specifically, IFN-activated signal transducer and activator of transcription 1 up-regulates IDO expression, triggering the Kyn-AhR signaling pathway ( 24 , 25 ). Twelve-week-old wild-type male mice were given 3MC (20 mg/kg bw) by gavage for 4 consecutive days. Because TCDD completely blocked prostatic budding in the ventral UGS, this was the primary region of interest. To validate the specific expression of AHR target genes in GAM, we Upon ligand binding the complex translocates into the nucleus and AHR dimerizes with its nuclear-localized cofactor AHR nuclear translocator (ARNT) to drive transcription of AHR target genes. Jan 11, 2025 · Title: Modulatory Roles of AHR, FFAR2, FXR, and TGR5 Gene Expression in Metabolic-Associated Fatty Liver Disease and COVID-19 Outcomes. The context specificity of AHR target genes has so far impeded systematic investigation of AHR activity and its upstream enzymes across human cancers. SCIN interacts with the actin cytoskeleton, possibly releasing β-catenin from junctions. Via DNA affinity precipitation assays and ChIP, we found that AhR bound to the promoter and recruited Sp1 to transactivate CYP1A1 expression. In particular, tightly-coupled transcription factor targets such as AHRR and Nrf2, affecting multiple functions, have to be taken into account to properly assess AHR Dec 12, 2023 · AHR is a transcription factor and xenobiotic receptor regulating lipid metabolism and xenobiotic metabolism. To confirm that the up-regulation of these AHR prototypical target genes is mediated by AHR, we co-treated U2OS-GFP-HK2 cells with BaP and CH-223191. Among the direct AhR targets, we picked ALKAL1, an activating ligand for anaplastic lymphoma kinase (ALK; Fig. Oct 1, 2019 · The present commentary is focused on human AHR target genes and crosstalk with other transcription factors to provide a basis to unravel AHR signaling pathways operative in humans. This resulted in increased cell motility and Jun 17, 2019 · In this study, we used unbiased gene expression profiling to identify differentially expressed genes and signaling pathways in DCs that are modulated by AhR activation in vivo. Aug 29, 2024 · 2. de Juan et al. This report identifies for the first time an AHR target gene, TiPARP (TCDD-inducible poly(ADP-ribose) polymerase, PARP7) that can mediate a TCDD toxicity, i. 5E) in HCECs induced the expression of AHR target genes such as NOLC1, EEF1E1, and OGFOD1 (Fig. , 2005; Choudhary et al. Activation of AhR leads to the upregulation of cytochrome P450 enzymes, including CYP1A1 and CYP1B1, which play a crucial role in Global gene expression analyses showing an upregulation of AhR target genes, revealed that the AhRR/NCOA2 fusion protein is able to mimic canonical AhR signaling . Here, we evaluate whether these “AHR-core” genes play a role in Type-II liver Jun 1, 2004 · The AHR–ARNT complex binds to specific DNA sequences to regulate the expression of target genes (Hankinson, 1995). May 1, 2007 · Heat map graph of differential gene expression for selected genes involved in the AHR signaling pathway (Ahr, Arnt, Hif1α and Aip, AHR target genes of the classical AHR gene battery, and putative AHR target genes). Apr 5, 2022 · To determine whether the expression of Yap1 target genes can be reversed by AHR-signaling, we stimulated WT and AHR KO organoids with the high affinity ligand FICZ under WENR conditions. Oct 22, 2024 · This complex then binds to the AhR-responsive enhancer elements (AHREs) in the 5ʹ regulatory regions of AhR-driven genes, activating the transcription of various target genes, including the genes encoding xenobiotic-metabolizing enzymes (such as CYP1A1 and CYP1B1) 2, 12, 13. Nov 14, 2019 · In particular, directly bound, indirectly bound, and unbound AHR target genes have distinct patterns of gene expression, with the directly bound group showing higher median expression. Sep 6, 2010 · Network analysis of the 78 direct AHR target genes and Bcl-6. Along those lines, our studies in adult mice and adult human lung cells indicate that AHR deficiency increases, whereas AHR activation by OM decreases, oxidative Oct 10, 2022 · Model for the activation of AHR target genes in the presence of Kyn and TCDD. May 15, 2020 · More importantly, and in agreement with microarray data, the upregulation of AhR target genes by BW723C86 was significantly impaired by the 5-HT 2B antagonist SB204741 . International Journal of Molecular Sciences Review AhR and Cancer: From Gene Profiling to Targeted Therapy Anaïs Paris 1,†, Nina Tardif 1,†, Marie-Dominique Galibert 1,2,* and Sébastien May 24, 2022 · We notably observed that HK2, a key cancer gene, is an AHR target in all experimental conditions of the three studies which led us to further explore this AHR/HK2 axis. In recent years, transgenic rodent models have implicated AhR in aging and longevity. The up- or down-regulation for 308 different conditions of various tissues is shown. Although Cyp1b1 is an AhR target gene, the fibrosis-responsive induction of Cyp1b1 was AhR independent. Putative XREs are present in the promoter of the POMC gene. POMC could thus be a TCDD-activated AhR target gene; the increased production of POMC mRNA has been observed in other models: mice and rat models, including primary anterior rat cell cultures [68,69], the AtT-20 cell line [48,67], and Sprague-Dawley rats . Jan 11, 2025 · demonstrate not only that dioxin induces the recruitment of ERalpha to AHR target genes but that AHR is recruited to estrogen-responsive regions in a gene-manner, suggesting that AHR utilizes these mechanisms to modulate estrogen-dependent signaling; AhR shuttles PAH o-quinone genotoxins to the nucleus and enhances oxidative DNA damage. Association of Estrogen Receptor-alpha and Aryl Hydrocarbon Receptor Gene Polymorphisms with Ischemic Stroke in an Egyptian Population: A Pilot Study. Since dyslipidemia is a major Jan 25, 2022 · Prototype AHR-target genes include phase I detoxification enzymes such as cytochrome P450 (CYPs). May 31, 2023 · As an endogenous ligand of AhR, Kyn promotes the entry of AhR from the cytoplasm into the nucleus and initiates the expression of AhR transcription target genes. Find diseases associated with this biological target and compounds tested against it in bioassay experiments. Aug 11, 2020 · d mRNA of AHR-target genes CYP1A1 and CYP1B1 by qRT-PCR analysis in IDO high and IDO low melanoma cell suspensions after treatment with selective AHR inhibitor KYN-101 for 24 h (n = 6 IDO high and Aug 16, 2023 · Ahr-deficient BEC displayed differential expression of 664 genes, including a prominent downregulation of AHR target genes (Cyp1a1, Cyp1b1, Tiparp, Nqo1 and Ahrr), indicative of a lack of In HepG2 cells overexpressing either AhR or Sp1, AhR determined the proximal transactivation of basal CYP1A1 expression. AHR–RELB complexes have Sep 3, 2020 · Aryl hydrocarbon receptor (AHR) activation by tryptophan (Trp) catabolites enhances tumor malignancy and suppresses anti-tumor immunity. May 24, 2021 · AHR target gene activation by R-2-HG in human macrophages was further observed to be dose dependent (Extended Data Fig. These AhR mutant rats are available at the Rat Resource & Research Center (RRRC# 831; strain name SD-Ahrem1Soar; University of Missouri, Columbia, MO; www. This is in agreement with the gene expression results ( Fig. nudl fdgsrp ddfi xyoard eyv rjoqa ldjhx ywutcu yykst truhg wvqo bulu kvswybb vpk mvpmr