Global transcriptional regulation of innate immunity by ATF-7 in C. elegans
Author(s)Fletcher, Marissa; Tillman, Erik J.; Butty, Vincent L.; Levine, Stuart S.; Kim, Dennis H.
MetadataShow full item record
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.
DepartmentMassachusetts Institute of Technology. Department of Biology
Public Library of Science (PLoS)
Fletcher, Marissa et al. “Global transcriptional regulation of innate immunity by ATF-7 in C. elegans.” PLOS genetics 15 (2019): e1007830 © 2019 The Author(s)
Final published version