genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in c. elegans基因表达的遗传和生理激活osmosensitive模仿转录签名秀丽隐杆线虫的病原体感染.pdfVIP

Genetic and Physiological Activation of Osmosensitive Gene Expression Mimics Transcriptional Signatures of Pathogen Infection in C. elegans 1 1 2 1 Anne-Katrin Rohlfing , Yana Miteva , Sridhar Hannenhalli , Todd Lamitina * 1 Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 2 Department of Genetics, Penn Center for Bioinformatics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Abstract The soil-dwelling nematode C. elegans is a powerful system for comparative molecular analyses of environmental stress response mechanisms. Infection of worms with bacterial and fungal pathogens causes the activation of well-characterized innate immune transcriptional programs in pathogen-exposed hypodermal and intestinal tissues. However, the pathophysiological events that drive such transcriptional responses are not understood. Here, we show that infection- activated transcriptional responses are, in large part, recapitulated by either physiological or genetic activation of the osmotic stress response. Microarray profiling of wild type worms exposed to non-lethal hypertonicity identified a suite of genes that were also regulated by infection. Expression profiles of five different osmotic stress resistant (osr) mutants under isotonic conditions reiterated the wild type transcriptional response to osmotic stress and also showed substantial similarity to infection-induced gene expression under isotonic conditions. Computational, transgenic, and functional approaches revealed that two GATA transcription factors previously implicated in infection-induced transcriptional responses, elt-2 and elt-3, are also