Deconvolution of multiplexed transcriptional responses to wood smoke particles defines rapid aryl hydrocarbon receptor signaling dynamics
| Autor: | Margaret Gruca, Anthony N. Gerber, Arnav Gupta, Sarah K. Sasse, Lynn Sanford, Robin D. Dowell |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Transcription
Genetic nascent transcription air pollution ROI region of interest TCDD 2 3 7 8-tetrachlorodibenzo-p-dioxin Enhancer RNAs ATAC-seq PRO-Seq precision nuclear run-on sequencing Biochemistry Mice AHR aryl hydrocarbon receptor eRNA enhancer RNA Smoke ATAC-Seq assay for transposase-accessible chromatin using sequencing Basic Helix-Loop-Helix Transcription Factors DNA (Cytosine-5-)-Methyltransferases Cell Line Transformed biology Chemistry aryl hydrocarbon receptor AHRR AHR repressor IL-24 interleukin-24 NF-kappa B respiratory system Wood Chromatin Cell biology ChIP chromatin immunoprecipitation XRE xenobiotic response element Signal Transduction Research Article NIH the National Institutes of Health IGV Integrative Genomics Viewer PM particulate matter Chromatin remodeling TCF ternary response factor lung TFEA transcription factor enrichment analysis Cytochrome P-450 CYP1A1 Animals Humans Enhancer Molecular Biology Transcription factor PAH polyaromatic hydrocarbon Cell Biology smAEC small airway epithelial cell WSP wood smoke particle Aryl hydrocarbon receptor Chromatin Assembly and Disassembly SRF serum response factor Repressor Proteins Receptors Aryl Hydrocarbon biology.protein NIH 3T3 Cells chromatin enhancer qPCR quantitative PCR Chromatin immunoprecipitation |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | The heterogeneity of respirable particulates and compounds complicates our understanding of transcriptional responses to air pollution. Here, we address this by applying precision nuclear run-on sequencing and the assay for transposase-accessible chromatin sequencing to measure nascent transcription and chromatin accessibility in airway epithelial cells after wood smoke particle (WSP) exposure. We used transcription factor enrichment analysis to identify temporally distinct roles for ternary response factor–serum response factor complexes, the aryl hydrocarbon receptor (AHR), and NFκB in regulating transcriptional changes induced by WSP. Transcription of canonical targets of the AHR, such as CYP1A1 and AHRR, was robustly increased after just 30 min of WSP exposure, and we discovered novel AHR-regulated pathways and targets including the DNA methyltransferase, DNMT3L. Transcription of these genes and associated enhancers rapidly returned to near baseline by 120 min after exposure. The kinetics of AHR- and NFκB-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 NFκB-mediated responses through 120 min of exposure. 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 NFκB signaling in controlling proinflammatory gene expression. This work also defines an integrated genomics-based strategy for deconvoluting multiplexed transcriptional responses to heterogeneous environmental exposures. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|