The Developmental Intestinal Regulator ELT-2 Controls P38-Dependent Immune Responses in Adult C. Elegans

Overview

Journal PLoS Genet

Specialty Genetics

Date 2015 May 29

PMID 26016853

Citations 30

Authors

Dena H S Block

Kwame Twumasi-Boateng

Hae Sung Kang

Jolie A Carlisle

Alexandru Hanganu

Ty Yu-Jen Lai

Michael Shapira

Affiliations

Soon will be listed here.

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.

Citing Articles

The Roles of Distinct Transcriptional Factors in the Innate Immunity of .

Afridi M, Tu H Cells. 2025; 14(5).

PMID: 40072056 PMC: 11899719. DOI: 10.3390/cells14050327.

In vivo pulse-chase in reveals intestinal histone turnover changes upon starvation.

Borchers C, Osburn K, Roh H, Aoki S bioRxiv. 2025; .

PMID: 39990428 PMC: 11844474. DOI: 10.1101/2025.02.13.638128.

The proteome response to two protective symbionts.

Pees B, Peters L, Treitz C, Hamerich I, Kissoyan K, Tholey A mBio. 2024; 15(4):e0346323.

PMID: 38411078 PMC: 11005407. DOI: 10.1128/mbio.03463-23.

Domain definition and preliminary functional exploration of the endonuclease NOBP-1 in Strongyloides stercoralis.

Zhou H, Yuan W, Lei W, Zhou T, Qin P, Zhang B Parasit Vectors. 2023; 16(1):399.

PMID: 37924155 PMC: 10623843. DOI: 10.1186/s13071-023-05940-9.

Transcriptome profiling of the Caenorhabditis elegans intestine reveals that ELT-2 negatively and positively regulates intestinal gene expression within the context of a gene regulatory network.

Williams R, King D, Mastroianni I, Hill J, Apenes N, Ramirez G Genetics. 2023; 224(4).

PMID: 37183501 PMC: 10411582. DOI: 10.1093/genetics/iyad088.

References

Gerstein M, Lu Z, Van Nostrand E, Cheng C, Arshinoff B, Liu T . Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science. 2010; 330(6012):1775-87. PMC: 3142569. DOI: 10.1126/science.1196914. View

Fukushige T, Hawkins M, McGhee J . The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine. Dev Biol. 1998; 198(2):286-302. View

Shapira M, Hamlin B, Rong J, Chen K, Ronen M, Tan M . A conserved role for a GATA transcription factor in regulating epithelial innate immune responses. Proc Natl Acad Sci U S A. 2006; 103(38):14086-91. PMC: 1599916. DOI: 10.1073/pnas.0603424103. View

van der Hoeven R, McCallum K, Cruz M, Garsin D . Ce-Duox1/BLI-3 generated reactive oxygen species trigger protective SKN-1 activity via p38 MAPK signaling during infection in C. elegans. PLoS Pathog. 2012; 7(12):e1002453. PMC: 3245310. DOI: 10.1371/journal.ppat.1002453. View

Schulenburg H, Hoeppner M, Weiner 3rd J, Bornberg-Bauer E . Specificity of the innate immune system and diversity of C-type lectin domain (CTLD) proteins in the nematode Caenorhabditis elegans. Immunobiology. 2008; 213(3-4):237-50. DOI: 10.1016/j.imbio.2007.12.004. View

Pujol N, Zugasti O, Wong D, Couillault C, Kurz C, Schulenburg H . Anti-fungal innate immunity in C. elegans is enhanced by evolutionary diversification of antimicrobial peptides. PLoS Pathog. 2008; 4(7):e1000105. PMC: 2453101. DOI: 10.1371/journal.ppat.1000105. View

Garsin D, Sifri C, Mylonakis E, Qin X, Singh K, Murray B . A simple model host for identifying Gram-positive virulence factors. Proc Natl Acad Sci U S A. 2001; 98(19):10892-7. PMC: 58570. DOI: 10.1073/pnas.191378698. View

Molkentin J . The zinc finger-containing transcription factors GATA-4, -5, and -6. Ubiquitously expressed regulators of tissue-specific gene expression. J Biol Chem. 2000; 275(50):38949-52. DOI: 10.1074/jbc.R000029200. View

Twumasi-Boateng K, Wang T, Tsai L, Lee K, Salehpour A, Bhat S . An age-dependent reversal in the protective capacities of JNK signaling shortens Caenorhabditis elegans lifespan. Aging Cell. 2012; 11(4):659-67. PMC: 3440580. DOI: 10.1111/j.1474-9726.2012.00829.x. View

10.

McGhee J, Sleumer M, Bilenky M, Wong K, McKay S, Goszczynski B . The ELT-2 GATA-factor and the global regulation of transcription in the C. elegans intestine. Dev Biol. 2006; 302(2):627-45. DOI: 10.1016/j.ydbio.2006.10.024. View

11.

Troemel E, Chu S, Reinke V, Lee S, Ausubel F, Kim D . p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genet. 2006; 2(11):e183. PMC: 1635533. DOI: 10.1371/journal.pgen.0020183. View

12.

Shivers R, Pagano D, Kooistra T, Richardson C, Reddy K, Whitney J . Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38 MAPK regulates innate immunity in Caenorhabditis elegans. PLoS Genet. 2010; 6(4):e1000892. PMC: 2848548. DOI: 10.1371/journal.pgen.1000892. View

13.

Morisco C, Seta K, Hardt S, Lee Y, Vatner S, Sadoshima J . Glycogen synthase kinase 3beta regulates GATA4 in cardiac myocytes. J Biol Chem. 2001; 276(30):28586-97. DOI: 10.1074/jbc.M103166200. View

14.

Youngman M, Rogers Z, Kim D . A decline in p38 MAPK signaling underlies immunosenescence in Caenorhabditis elegans. PLoS Genet. 2011; 7(5):e1002082. PMC: 3098197. DOI: 10.1371/journal.pgen.1002082. View

15.

Lee S, Wong R, Chin C, Lim T, Eng S, Kong C . Burkholderia pseudomallei suppresses Caenorhabditis elegans immunity by specific degradation of a GATA transcription factor. Proc Natl Acad Sci U S A. 2013; 110(37):15067-72. PMC: 3773767. DOI: 10.1073/pnas.1311725110. View

16.

Tan M, Ausubel F . Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci U S A. 1999; 96(2):715-20. PMC: 15202. DOI: 10.1073/pnas.96.2.715. View

17.

Boulin T, Etchberger J, Hobert O . Reporter gene fusions. WormBook. 2007; :1-23. PMC: 4781452. DOI: 10.1895/wormbook.1.106.1. View

18.

Gardner P . Superoxide production by the mycobacterial and pseudomonad quinoid pigments phthiocol and pyocyanine in human lung cells. Arch Biochem Biophys. 1996; 333(1):267-74. DOI: 10.1006/abbi.1996.0390. View

19.

Fraiture M, Brunner F . Killing two birds with one stone: trans-kingdom suppression of PAMP/MAMP-induced immunity by T3E from enteropathogenic bacteria. Front Microbiol. 2014; 5:320. PMC: 4105635. DOI: 10.3389/fmicb.2014.00320. View

20.

Ausubel F . Are innate immune signaling pathways in plants and animals conserved?. Nat Immunol. 2005; 6(10):973-9. DOI: 10.1038/ni1253. View