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

Autor: Marissa Fletcher, Erik J Tillman, Vincent L Butty, Stuart S Levine, Dennis H Kim
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: PLoS Genetics, Vol 15, Iss 2, p e1007830 (2019)
Druh dokumentu: article
ISSN: 1553-7390
1553-7404
DOI: 10.1371/journal.pgen.1007830
Popis: 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.
Databáze: Directory of Open Access Journals
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