Global transcriptional regulation of innate immunity by ATF-7 in C. elegans
Name
journal.pgen.1007830.pdf
Description
Published version
Size
1.98 MB
Format
Adobe PDF
Checksum (MD5)
2be11a8736017468b04fc9f95d8776b0
Author(s)
Fletcher, Marissa
Tillman, Erik J.
Butty, Vincent L.
Levine, Stuart S.
Kim, Dennis H.
Date Issued
February 2019
Journal
PLOS genetics
Publisher
Public Library of Science (PLoS)
Citation
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)
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1371/JOURNAL.PGEN.1007830
