ELT-2 is the predominant transcription factor controlling differentiation and function of the C. elegans intestine, from embryo to adult

Abstract

Starting with SAGE-libraries prepared from C. elegans FAC-sorted embryonic intestine cells (8E-16E cell stage), from total embryos and from purified oocytes, and taking advantage of the NextDB in situ hybridization data base, we define sets of genes highly expressed from the zygotic genome, and expressed either exclusively or preferentially in the embryonic intestine or in the intestine of newly hatched larvae; we had previously defined a similarly expressed set of genes from the adult intestine. We show that an extended TGATAA-like sequence is essentially the only candidate for a cis-acting regulatory motif common to intestine genes expressed at all stages. This sequence is a strong ELT-2 binding site and matches the sequence of GATA-like sites found to be important for the expression of every intestinal gene so far analyzed experimentally. We show that the majority of these three sets of highly expressed intestinal-specific/intestinal-enriched genes respond strongly to ectopic expression of ELT-2 within the embryo. By flow-sorting elt-2(null) larvae from elt-2(+) larvae and then preparing Solexa/Illumina-SAGE libraries, we show that the majority of these genes also respond strongly to loss-of-function of ELT-2. To test the consequences of loss of other transcription factors identified in the embryonic intestine, we develop a strain of worms that is RNAi-sensitive only in the intestine; however, we are unable (with one possible exception) to identify any other transcription factor whose intestinal loss-of-function causes a phenotype of comparable severity to the phenotype caused by loss of ELT-2. Overall, our results support a model in which ELT-2 is the predominant transcription factor in the post-specification C. elegans intestine and participates directly in the transcriptional regulation of the majority (> 80%) of intestinal genes. We present evidence that ELT-2 plays a central role in most aspects of C. elegans intestinal physiology: establishing the structure of the enterocyte, regulating enzymes and transporters involved in digestion and nutrition, responding to environmental toxins and pathogenic infections, and regulating the downstream intestinal components of the daf-2/daf-16 pathway influencing aging and longevity.

Burkholderia pseudomallei suppresses Caenorhabditis elegans immunity by specific degradation of a GATA transcription factor

“…Among the 1,122 genes identified as SMA-6 regulated (17), 144 of these overlapped with the B. pseudomallei infection response (Rf = 1.83). The GATA transcription factor ELT-2 is a positive regulator of intestinal immune responses (1,18). A significant enrichment (Rf = 8.43, hypergeometric probability P < 1 × 10 −6 ) was observed between ELT-2-regulated genes (19) and B. pseudomallei infection response genes, suggesting that ELT-2 might also contribute to the infection response of B. pseudomallei (Fig.…”

Physiological and molecular mechanisms of salt and water homeostasis in the nematodeCaenorhabditis elegans

“…While these findings establish the requirement for these two GATA factors, it is still unclear what role they serve in osmosensitive gene expression. Importantly, elt-2 and elt-3 appear to be generally required for expression of numerous genes in the intestine and hypodermis, respectively (31,51,(73)(74). Therefore, it is unclear whether either factor is induced by osmotic stress like NFAT5/TonEBP or whether they simply serve as tissue specifying cofactors for a yet to be identified osmotically inducible factor.…”

Intermediate filaments in Caenorhabditis elegans

“…The C. elegans intestine is a ''simple'' epithelial tube consisting only of 20 polarized and tightly-associated cells which are, however, subject to multiple patterning and morphogenetic events [McGhee, 2007;McGhee et al, 2009]. We will show that intestinal morphogenesis and function can serve as examples of the interplay between IFs and other cytoskeletal filaments and their integration into a transcellular network by adherens-type cell-cell junctions.…”