The Developmental Intestinal Regulator ELT-2 Controls p38-Dependent Immune Responses in Adult C. elegans

PLoS Genet. 2015 May 27;11(5):e1005265. doi: 10.1371/journal.pgen.1005265. eCollection 2015 May.

Abstract

GATA transcription factors play critical roles in cellular differentiation and development. However, their roles in mature tissues are less understood. In C. elegans larvae, the transcription factor ELT-2 regulates terminal differentiation of the intestine. It is also expressed in the adult intestine, where it was suggested to maintain intestinal structure and function, and where it was additionally shown to contribute to infection resistance. To study the function of elt-2 in adults we characterized elt-2-dependent gene expression following its knock-down specifically in adults. Microarray analysis identified two ELT-2-regulated gene subsets: one, enriched for hydrolytic enzymes, pointed at regulation of constitutive digestive functions as a dominant role of adult elt-2; the second was enriched for immune genes that are induced in response to Pseudomonas aeruginosa infection. Focusing on the latter, we used genetic analyses coupled to survival assays and quantitative RT-PCR to interrogate the mechanism(s) through which elt-2 contributes to immunity. We show that elt-2 controls p38-dependent gene induction, cooperating with two p38-activated transcription factors, ATF-7 and SKN-1. This demonstrates a mechanism through which the constitutively nuclear elt-2 can impact induced responses, and play a dominant role in C. elegans immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factors / genetics
  • Activating Transcription Factors / metabolism
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / immunology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • GATA Transcription Factors / genetics
  • GATA Transcription Factors / metabolism*
  • Gene Expression Regulation*
  • Gene Knockdown Techniques
  • Immunity, Innate / genetics*
  • Intestinal Mucosa / metabolism*
  • Larva / genetics
  • Larva / metabolism
  • Promoter Regions, Genetic
  • Pseudomonas aeruginosa
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • ATF-7 protein, C elegans
  • Activating Transcription Factors
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • ELT-2 protein, C elegans
  • GATA Transcription Factors
  • Transcription Factors
  • skn-1 protein, C elegans
  • p38 Mitogen-Activated Protein Kinases

Associated data

  • GEO/GSE63846

Grant support

This research was supported by the Ellison Medical Foundation. In addition, HSK was supported by the Berkeley Biology Fellows Program, JAC was supported by an Amgen scholarship, and KTB was supported by a Post Graduate Scholarship from the Natural Sciences and Engineering Research Council of Canada. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.