Global transcriptional regulation of innate immunity by ATF-7 in C. elegans

PLoS Genet. 2019 Feb 21;15(2):e1007830. doi: 10.1371/journal.pgen.1007830. eCollection 2019 Feb.

Abstract

The nematode Caenorhabditis elegans has emerged as a genetically tractable animal host in which to study evolutionarily conserved mechanisms of innate immune signaling. We previously showed that the PMK-1 p38 mitogen-activated protein kinase (MAPK) pathway regulates innate immunity of C. elegans through phosphorylation of the CREB/ATF bZIP transcription factor, ATF-7. Here, we have undertaken a genomic analysis of the transcriptional response of C. elegans to infection by Pseudomonas aeruginosa, combining genome-wide expression analysis by RNA-seq with ATF-7 chromatin immunoprecipitation followed by sequencing (ChIP-Seq). We observe that PMK-1-ATF-7 activity regulates a majority of all genes induced by pathogen infection, and observe ATF-7 occupancy in regulatory regions of pathogen-induced genes in a PMK-1-dependent manner. Moreover, functional analysis of a subset of these ATF-7-regulated pathogen-induced target genes supports a direct role for this transcriptional response in host defense. The genome-wide regulation through PMK-1- ATF-7 signaling reveals a striking level of control over the innate immune response to infection through a single transcriptional regulator.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factors / metabolism*
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / immunology*
  • Caenorhabditis elegans / microbiology*
  • Caenorhabditis elegans Proteins / metabolism*
  • Chromatin Immunoprecipitation
  • Gene Expression Profiling / methods
  • Gene Expression Regulation
  • Genome-Wide Association Study
  • Immunity, Innate
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinases / metabolism
  • Pseudomonas aeruginosa / immunology*
  • Sequence Analysis, RNA

Substances

  • ATF-7 protein, C elegans
  • Activating Transcription Factors
  • Caenorhabditis elegans Proteins
  • Mitogen-Activated Protein Kinases
  • Pmk-1 protein, C elegans