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

PLoS Genetics
Marissa FletcherDennis H Kim

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.

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Citations

Apr 14, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wenwen ZhangJun Zheng
Aug 13, 2020·Journal of Neurogenetics·Dennis H Kim, Steven W Flavell
Aug 29, 2020·PLoS Pathogens·Yi-Cheng MaKe-Qin Zhang
Dec 12, 2020·Developmental Biology·Chee Kiang EweJoel H Rothman
Feb 26, 2021·Cellular and Molecular Life Sciences : CMLS·Juan A Garcia-SanchezOrane Visvikis
Mar 19, 2021·Microbiology and Molecular Biology Reviews : MMBR·Leah J Radeke, Michael A Herman
Sep 30, 2021·Life Science Alliance·Sonja K SooJeremy M Van Raamsdonk
Oct 9, 2021·Biochemical Society Transactions·Benjamin W Harding, Jonathan J Ewbank

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Datasets Mentioned

BETA
GSE119294
GSE119292
GSE119293

Methods Mentioned

BETA
dissection
RNA-seq
ChIP-seq
immunoprecipitation
ChIP
pull-down
Assay

Software Mentioned

genomeDir
MEME
bedtools intersect
DAVID
macs2
samtools
gene set enrichment analysis ( GSEA )
Gene Set Enrichment Analysis ( GSEA
TranscriptomeSAM
ngs

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