Show simple item record

dc.contributor.authorPeterson, Nicholas D.
dc.contributor.authorCheesman, Hilary K.
dc.contributor.authorAnderson, Sarah M.
dc.contributor.authorFoster, Kyle J.
dc.contributor.authorChhaya, Richa
dc.contributor.authorPerrat, Paola N.
dc.contributor.authorThekkiniath, Jose
dc.contributor.authorYang, Qiyuan
dc.contributor.authorHaynes, Cole M
dc.contributor.authorPukkila-Worley, Read
dc.date2022-08-11T08:09:52.000
dc.date.accessioned2022-08-23T16:46:37Z
dc.date.available2022-08-23T16:46:37Z
dc.date.issued2019-01-22
dc.date.submitted2019-02-28
dc.identifier.citation<p>PLoS Genet. 2019 Jan 22;15(1):e1007935. doi: 10.1371/journal.pgen.1007935. eCollection 2019 Jan. <a href="https://doi.org/10.1371/journal.pgen.1007935">Link to article on publisher's site</a></p>
dc.identifier.issn1553-7390 (Linking)
dc.identifier.doi10.1371/journal.pgen.1007935
dc.identifier.pmid30668573
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40916
dc.description.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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30668573&dopt=Abstract">Link to Article in PubMed</a></p>
dc.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.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCaenorhabditis elegans
dc.subjectPseudomonas aeruginosa
dc.subjectImmune response
dc.subjectBacterial pathogens
dc.subjectDNA transcription
dc.subjectTranscriptional control
dc.subjectSequence motif analysis
dc.subjectMAPK signaling cascades
dc.subjectBacteria
dc.subjectGenetics and Genomics
dc.subjectImmunology and Infectious Disease
dc.subjectMicrobiology
dc.titleThe nuclear hormone receptor NHR-86 controls anti-pathogen responses in C. elegans
dc.typeJournal Article
dc.source.journaltitlePLoS genetics
dc.source.volume15
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4728&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3716
dc.identifier.contextkey13921319
refterms.dateFOA2022-08-23T16:46:37Z
html.description.abstract<p>Nuclear 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.</p>
dc.identifier.submissionpathoapubs/3716
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.contributor.departmentNeurobiology
dc.contributor.departmentMolecular, Cell and Cancer Biology
dc.contributor.departmentProgram in Innate Immunity
dc.contributor.departmentMedicine
dc.source.pagese1007935
dc.contributor.studentPaola Perrat
dc.description.thesisprogramNeuroscience


Files in this item

Thumbnail
Name:
journal.pgen.1007935.pdf
Size:
2.641Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

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.
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.