The nuclear hormone receptor NHR-86 controls anti-pathogen responses in C. elegans
AuthorsPeterson, Nicholas D.
Cheesman, Hilary K.
Anderson, Sarah M.
Foster, Kyle J.
Perrat, Paola N.
Haynes, Cole M.
Student AuthorsPaola Perrat
UMass Chan AffiliationsGraduate School of Biomedical Sciences
Molecular, Cell and Cancer Biology
Program in Innate Immunity
Document TypeJournal Article
Sequence motif analysis
MAPK signaling cascades
Genetics and Genomics
Immunology and Infectious Disease
MetadataShow full item record
AbstractNuclear hormone receptors (NHRs) are ligand-gated transcription factors that control adaptive host responses following recognition of specific endogenous or exogenous ligands. Although NHRs have expanded dramatically in C. elegans compared to other metazoans, the biological function of only a few of these genes has been characterized in detail. Here, we demonstrate that an NHR can activate an anti-pathogen transcriptional program. Using genetic epistasis experiments, transcriptome profiling analyses and chromatin immunoprecipitation-sequencing, we show that, in the presence of an immunostimulatory small molecule, NHR-86 binds to the promoters of immune effectors to activate their transcription. NHR-86 is not required for resistance to the bacterial pathogen Pseudomonas aeruginosa at baseline, but activation of NHR-86 by this compound drives a transcriptional program that provides protection against this pathogen. Interestingly, NHR-86 targets immune effectors whose basal regulation requires the canonical p38 MAPK PMK-1 immune pathway. However, NHR-86 functions independently of PMK-1 and modulates the transcription of these infection response genes directly. These findings characterize a new transcriptional regulator in C. elegans that can induce a protective host response towards a bacterial pathogen.
PLoS Genet. 2019 Jan 22;15(1):e1007935. doi: 10.1371/journal.pgen.1007935. eCollection 2019 Jan. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40916
RightsCopyright: © 2019 Peterson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright: © 2019 Peterson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.