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

Dena H S Block; Kwame Twumasi-Boateng; Hae Sung Kang; Jolie A Carlisle; Alexandru Hanganu; Ty Yu-Jen Lai; Michael Shapira

doi:10.1371/journal.pgen.1005265

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.

Authors

Dena H S Block¹, Kwame Twumasi-Boateng², Hae Sung Kang¹, Jolie A Carlisle¹, Alexandru Hanganu¹, Ty Yu-Jen Lai¹, Michael Shapira²

Affiliations

¹ Department of Integrative Biology, University of California, Berkeley, Berkeley, California, United States of America.
² Department of Integrative Biology, University of California, Berkeley, Berkeley, California, United States of America; Graduate Group in Microbiology, University of California Berkeley, Berkeley, California, United States of America.

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

Grants and funding

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.