A 44 bp intestine-specific hermaphrodite-specific enhancer from the C. elegans vit-2 vitellogenin gene is directly regulated by ELT-2, MAB-3, FKH-9 and DAF-16 and indirectly regulated by the germline, by daf-2 /insulin signaling and by the TGF-β/Sma/Mab pathway

Abstract

The Caenorhabditis elegans vitellogenin genes are transcribed in the intestine of adult hermaphrodites but not of males. A 44-bp region from the vit-2 gene promoter is able largely to reconstitute this tissue-, stage- and sex-specific-expression. This "enhancer" contains a binding site for the DM-domain factor MAB-3, the male-specific repressor of vitellogenesis, as well as an activator site that we show is the direct target of the intestinal GATA factor ELT-2. We further show that the enhancer is directly activated by the winged-helix/forkhead-factor FKH-9, (whose gene has been shown by others to be a direct target of DAF-16), by an unknown activator binding to the MAB-3 site, and by the full C. elegans TGF-β/Sma/Mab pathway acting within the intestine. The vit-2 gene has been shown by others to be repressed by the daf-2/daf-16 insulin signaling pathway, which so strongly influences aging and longevity in C. elegans. We show that the activity of the 44 bp vit-2 enhancer is abolished by loss of daf-2 but is restored by simultaneous loss of daf-16. DAF-2 acts from outside of the intestine but DAF-16 acts both from outside of the intestine and from within the intestine where it binds directly to the same non-canonical target site that interacts with FKH-9. Activity of the 44 bp vit-2 enhancer is also inhibited by loss of the germline, in a manner that is only weakly influenced by DAF-16 but that is strongly influenced by KRI-1, a key downstream effector in the pathway by which germline loss increases C. elegans lifespan. The complex behavior of this enhancer presumably allows vitellogenin gene transcription to adjust to demands of body size, germline proliferation and nutritional state but we suggest that the apparent involvement of this enhancer in aging and longevity "pathways" could be incidental.

Vitellogenins - Yolk Gene Function and Regulation in Caenorhabditis elegans

“…There are six vitellogenin genes in the C. elegans genome (Figure 1). vit-2 , the best-studied of the vitellogenins (Goszczynski et al, 2016), encodes YP170B. vit-1 is 82% identical to vit-2 .…”

“…As the metabolic cost of abundant vitellogenin expression must be staggering, fine-tuning of their expression is paramount; hence multiple regulatory inputs exist, integrating signals stemming from nutritional status, environmental conditions and extra-intestinal tissues (Figure 7). It has often been stated in the literature that the promoters of the vit genes are simple (e.g., MacMorris et al, 1992), but recent extensive genetic dissection has found multiple regulators and signaling pathways impinging directly and indirectly on only a small section of the promoter of vit-2 (Goszczynski et al, 2016), the most extensively studied of the vitellogenins.…”

CEH-60/PBX regulates vitellogenesis and cuticle permeability through intestinal interaction with UNC-62/MEIS in Caenorhabditis elegans

“…elegans are known to respectively affect vit transcription and yolk provisioning to embryos [7–9], indicating that environmental cues play a role in regulating yolk protein production. Several intestinal transcription factors, including UNC-62 ( unc oordinated), ELT-2 ( e rythroid- l ike t ranscription factor), and MAB-3 ( m ale ab normal), bind directly to the promoter region of vit genes [9,10]. In earlier work, we recovered mutants of a transcription factor, CEH-60 ( C. elegans h omeobox), that produced almost no yolk proteins.…”

Linking Gene Expression in the Intestine to Production of Gametes Through the Phosphate Transporter PITR-1 inCaenorhabditis elegans

“…Expression of vit-2 in adult hermaphrodite intestinal cells is regulated through a concerted action of elt-2 and mab-3 . Additionally, the degree of vit-2 expression is modulated by multiple signaling pathways, including insulin signaling and TGFβ/Sma/Mab pathways (Goszczynski et al 2016). Our data suggest that pitr-1 could similarly be involved in modulating vit-2 transcription, possibly via nutritional status signaling from germline to intestine initiated by low Pi in germ cells.…”