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

<div><p>GATA transcription factors play critical roles in cellular differentiation and development. However, their roles in mature tissues are less understood. In <i>C</i>. <i>elegans</i> 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 <i>elt-2</i> in adults we characterized <i>elt-2</i>-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 <i>elt-2</i>; the second was enriched for immune genes that are induced in response to <i>Pseudomonas aeruginosa</i> infection. Focusing on the latter, we used genetic analyses coupled to survival assays and quantitative RT-PCR to interrogate the mechanism(s) through which <i>elt-2</i> contributes to immunity. We show that <i>elt-2</i> 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 <i>elt-2</i> can impact induced responses, and play a dominant role in <i>C</i>. <i>elegans</i> immunity.</p>