scholarly journals Aryl Hydrocarbon Receptor Directly Regulates Artemin Gene Expression

2019 ◽  
Vol 39 (20) ◽  
Author(s):  
Tomohiro Edamitsu ◽  
Keiko Taguchi ◽  
Eri H. Kobayashi ◽  
Ryuhei Okuyama ◽  
Masayuki Yamamoto
Keyword(s):  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Chromatin Immunoprecipitation ◽  
Active Form ◽  
Aryl Hydrocarbon ◽  
Xenobiotic Response Element ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Complex Regulation ◽  
Xenobiotic Response ◽  
Direct Induction

ABSTRACT Transgenic mice expressing a constitutively active form of the aryl hydrocarbon receptor in keratinocytes (AhR-CA mice) develop severe dermatitis that substantially recapitulates the pathology of human atopic dermatitis. The neurotrophic factor artemin (Artn) is highly expressed in the epidermis of AhR-CA mice and causes hypersensitivity to itch (alloknesis) by elongating nerves into the epidermis. However, whether the Artn gene is regulated directly by AhR or indirectly through complex regulation associated with AhR remains unclear. To this end, we previously conducted chromatin immunoprecipitation-sequencing analyses of the Artn locus and found a xenobiotic response element (XRE) motif located far upstream (52 kb) of the gene. Therefore, in this study, we addressed whether the XRE actually regulates the Artn gene expression by deleting the region containing the motif. We generated two lines of ArtnΔXRE mice. In the mouse epidermis, inducible expression of the Artn gene by the AhR agonist 3-methylcholanthrene was substantially suppressed compared to that in wild-type mice. Importantly, in AhR-CA::ArtnΔXRE mice, Artn expression was significantly suppressed, and alloknesis was improved. These results demonstrate that the Artn gene is indeed regulated by the distal XRE-containing enhancer, and alloknesis in AhR-CA mice is provoked by the AhR-mediated direct induction of the Artn gene.

scholarly journals Binding of an X-Specific Condensin Correlates with a Reduction in Active Histone Modifications at Gene Regulatory Elements

Genetics ◽  
2019 ◽  
Vol 212 (3) ◽  
pp. 729-742 ◽  
Author(s):  
Lena Annika Street ◽  
Ana Karina Morao ◽  
Lara Heermans Winterkorn ◽  
Chen-Yu Jiao ◽  
Sarah Elizabeth Albritton ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Chromatin Immunoprecipitation ◽  
Protein Complexes ◽  
Regulatory Elements ◽  
Evolutionarily Conserved ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Gene Regulatory Elements ◽  
Gene Regulatory ◽  
Regulatory Sites

Condensins are evolutionarily conserved protein complexes that are required for chromosome segregation during cell division and genome organization during interphase. In Caenorhabditis elegans, a specialized condensin, which forms the core of the dosage compensation complex (DCC), binds to and represses X chromosome transcription. Here, we analyzed DCC localization and the effect of DCC depletion on histone modifications, transcription factor binding, and gene expression using chromatin immunoprecipitation sequencing and mRNA sequencing. Across the X, the DCC accumulates at accessible gene regulatory sites in active chromatin and not heterochromatin. The DCC is required for reducing the levels of activating histone modifications, including H3K4me3 and H3K27ac, but not repressive modification H3K9me3. In X-to-autosome fusion chromosomes, DCC spreading into the autosomal sequences locally reduces gene expression, thus establishing a direct link between DCC binding and repression. Together, our results indicate that DCC-mediated transcription repression is associated with a reduction in the activity of X chromosomal gene regulatory elements.

scholarly journals Neuronal activity enhances aryl hydrocarbon receptor-mediated gene expression and dioxin neurotoxicity in cortical neurons

2008 ◽  
Vol 104 (5) ◽  
pp. 1415-1429 ◽  
Author(s):  
Chun-Hua Lin ◽  
Shu-Hui Juan ◽  
Chen Yu Wang ◽  
Yu-Yo Sun ◽  
Chih-Ming Chou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Neuronal Activity ◽  
Cortical Neurons ◽  
Aryl Hydrocarbon

scholarly journals Nascent RNA sequencing defines dynamic aryl hydrocarbon receptor signaling responses to wood smoke particles

2021 ◽  
Author(s):  
Arnav Gupta ◽  
Sarah K. Sasse ◽  
Lynn Sanford ◽  
Margaret A. Gruca ◽  
Robin D. Dowell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Airway Epithelial Cells ◽  
Wood Smoke ◽  
Primary Role ◽  
Airway Epithelial ◽  
Transcriptional Responses ◽  
Wildfire Smoke ◽  
Smoke Particles ◽  
Aryl Hydrocarbon

AbstractTranscriptional responses to wildfire smoke, an increasingly important cause of human morbidity, are poorly understood. Here, using a combination of precision nuclear run-on sequencing (PRO-seq) and the assay for transposase-accessible chromatin using sequencing (ATAC-seq), we identify rapid and dynamic changes in transcription and chromatin structure in Beas-2B airway epithelial cells after exposure to wood smoke particles (WSP). By comparing 30 and 120 minutes of WSP exposure, we defined three distinct temporal patterns of transcriptional induction and chromatin responses to WSP. Whereas transcription of canonical targets of the aryl hydrocarbon receptor (AHR), such as CYP1A1 and AHRR, was robustly increased after 30 minutes of WSP exposure, transcription of these genes and associated enhancers returned to near baseline at 120 minutes. ChIP-qPCR assays and AHR knockdown confirmed a role for AHR in regulating these transcriptional responses, and we applied bioinformatics approaches to identify novel AHR-regulated pathways and targets including the DNA methyltransferase, DNMT3L, and its interacting factor, SPOCD1. Our analysis also defined a role for NFkB as a primary transcriptional effector of WSP-induced changes in gene expression. The kinetics of AHR- and NFkB-regulated responses to WSP were distinguishable based on the timing of both transcriptional responses and chromatin remodeling, with induction of several cytokines implicated in maintaining the NFkB response. In aggregate, our data establish a direct and primary role for AHR in mediating airway epithelial responses to WSP and identify crosstalk between AHR and NFkB signaling in controlling pro-inflammatory gene expression.

Aryl Hydrocarbon Receptor Blocks Aging-Induced Senescence in the Liver and Fibroblast Cells

2021 ◽  
Author(s):  
Ana Nacarino-Palma ◽  
Eva M. Rico-Leo ◽  
Judith Campisi ◽  
Arvind Ramanathan ◽  
Jaime M. Merino ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Progenitor Cells ◽  
Chromatin Immunoprecipitation ◽  
Tissue Homeostasis ◽  
Fibroblast Cells ◽  
Aryl Hydrocarbon ◽  
Basal Expression ◽  
Repressive Effect ◽  
Secretory Phenotype ◽  
Mouse Lungs

ABSTRACTAging induces progressive organ degeneration and worsening of tissue homeostasis leading to multiple pathologies. Yet, little is known about the mechanisms and molecular intermediates involved. Here, we report that aged aryl hydrocarbon receptor-null mice (AhR-/-) had exacerbated senescence and larger numbers of liver progenitor cells. Senescence-associated markers β-galactosidase (SA-β-Gal), p16Ink4a and p21Cip1 and genes of the senescence-associated secretory phenotype (SASP) TNF and IL1 were overexpressed in aged AhR-/- livers. AhR binding to the promoter of those genes, as shown by chromatin immunoprecipitation, likely had a repressive effect maintaining their physiological levels in AhR+/+ livers. Furthermore, factors secreted by senescent cells MCP-2, MMP12 and FGF were also produced at higher levels in aged AhR-null livers. Supporting the linkage between senescence and stemness, liver progenitor cells were more abundant in AhR-/- mice, which could probably contribute to their increased hepatocarcinoma burden. These roles of AhR are not liver-specific since adult and embryonic AhR-null fibroblasts acquired cellular senescence upon culturing with overexpression of SA-β-Gal, p16Ink4a and p21Cip1. Notably, depletion of senescent cells with the senolytic agent navitoclax restored basal expression of senescent markers in AhR-/- fibroblasts. Oppositely, senescence promoter palbociclib induced an AhR-null like phenotype in AhR+/+ fibroblasts. Moreover, doxycycline-induced senescence reduced AhR levels while depletion of p16Ink4a-expressing senescent cells restored basal AhR levels in mouse lungs. Thus, AhR is needed to restrict age-induced senescence, and such activity seems to correlate with a more differentiated phenotype and with increased resistance to liver tumorigenesis.

scholarly journals Transcriptional Regulation of gga-miR-451 by AhR:Arnt in Mycoplasma gallisepticum (HS Strain) Infection

2019 ◽  
Vol 20 (12) ◽  
pp. 3087 ◽  
Author(s):  
Yabo Zhao ◽  
Yali Fu ◽  
Yingfei Sun ◽  
Mengyun Zou ◽  
Xiuli Peng
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Chromatin Immunoprecipitation ◽  
Regulatory Region ◽  
Mycoplasma Gallisepticum ◽  
Luciferase Reporter ◽  
Binding Motif ◽  
Aryl Hydrocarbon ◽  
Transcriptional Regulatory ◽  
Reporter Assays ◽  
Transcriptional Regulatory Region

MicroRNAs (miRNAs) have been determined to be important regulators for pathogenic microorganism infection. However, it is largely unclear how miRNAs are triggered during pathogen infection. We previously reported that the up-regulation of gga-miR-451 negatively regulates the Mycoplasma gallisepticum (MG)-induced production of inflammatory cytokines via targeting tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein zeta (YWHAZ). The aim of this study was to investigate the mechanism regulating gga-miR-451 in MG infection in chickens. Analysis of gga-miR-451 precursor, pri-miR-451, and pre-miR-451 indicated that the regulation occurred transcriptionally. We also identified the transcriptional regulatory region of gga-miR-451 that contained consensus-binding motif for aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (Arnt) complex, which is known as the transcription factor that regulates gene expression. Luciferase reporter assays combined with chromatin immunoprecipitation (ChIP) demonstrated that AhR:Arnt bound directly to the promoter elements of gga-miR-451, which were responsible for gga-miR-451 transcription in the context of MG infection. Furthermore, upregulation of AhR:Arnt significantly induced gga-miR-451 and inhibited YWHAZ expression, suggesting that AhR:Arnt may play an anti-inflammatory role in MG infection. This discovery suggests that induced gga-miR-451 expression is modulated by AhR:Arnt in response to MG infection.

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