Transcriptional profiling in neurons of C. elegans : comparison between ahr-1 mutant and wild-type animals.

ABSTRACT: The Aryl hydrocarbon Receptor (AhR) is a transcription factor well known in vertebrate to play an essential role as xenobiotic sensor. On the contrary, no ligand has been identified to date for invertebrate AhR. In some model organisms such as D. melanogaster and C. elegans, AhR orthologs have physiological functions and their inability to bind prototypical ligands of vertebrate AhR such as tetrachlorodibenzo-p-dioxin (TCDD) suggests that the detoxification role of the receptor could be an adaptation acquired during evolution. To better understand the physiological roles of AhR, we studied AhR-1, the C. elegans ortholog and performed transcriptomic and metabolomic analysis respectively in neuronal cells expressing AhR-1 and in whole animals. Next, we designed a reporter system in order to investigate if the transcriptional activity of AhR-1 could be modulated. Cos-7 cells were transfected with AhR-1, its dimerization partner AhA-1 (C. elegans ARNT ortholog) and a Firefly luciferase gene under the control of the human cytochrome P450 1A1 promotor. The luciferase bioluminescence measurement allows the identification of C. elegans AhR-1 modulators. Transcriptional profiling in neurons expressing AhR-1 revealed 95 genes down-regulated, and 76 genes up-regulated in AhR-1 KO animals. These genes are associated with nervous system function (depleted) and fatty acid process, oxidative phosphorylation and glycolysis (enriched). Metabolomic profiling results indicate a role for AhR-1 in regulating several endogenous metabolic pathways: amino-acid metabolism, carbohydrate metabolism as well as fatty acid metabolism Then, with the COS-7 in vitro screening model, we identified positive and negative modulators such as bacterial, dietary or environmental compounds. Considering C. elegans environment, these results could be used to highlight the role of invertebrate AhR and identified new features in vertebrate AhR.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE195728 | GEO | 2022/06/01

REPOSITORIES: GEO