Garrigues, J.M. et al. (2019) International Worm Meeting "Rewiring of the heat-shock response by Helitrons."

Tsu, B.V., Daugherty, M.D., Garrigues, J.M., Pasquinelli, A.E.

[International Worm Meeting, 2019]

Heat-shock factor 1 (HSF-1) is a highly conserved transcription factor found in budding yeast through humans and serves as a key regulator of the heat-shock response (HSR). Upon HSR induction, activated HSF-1 binds well-conserved motifs (termed heat-shock elements, or HSEs) and drives expression of genes important for mediating heat stress, such as chaperones. Remarkably, we found that almost 2/3 of HSEs in the C. elegans genome reside within Helitrons, a type of DNA transposon. Since transposable elements are known to provide transcription factor binding sites to nearby genes, we investigated the activity of the HSE-rich Helitrons in C. elegans. Upon heat shock, Helitron-embedded HSEs display increased HSF-1 and RNA polymerase II (Pol II) occupancy as well as up-regulation of nearby protein-coding genes. Unlike evolutionarily conserved and canonical HSR target genes (controlled by Helitron-independent HSEs or Hin-HSEs), we found that Helitron-acquired HSEs (Hac-HSEs) control expression of specific G protein-coupled receptor (GPCR) and collagen genes. Examination of other genomes revealed significant numbers of Helitron-provided HSEs in all other Caenorhabditis species. Interestingly, we found that different genes appear to be co-opted into the HSR by species-specific Helitron insertions. In agreement with this, Hac-HSEs were associated with the differential regulation of otherwise homologous genes in response to heat shock in C. elegans versus C. briggsae. Furthermore, we found variability in Helitron position, and therefore heat-shock inducibility of individual genes, even among wild isolates of C. elegans, suggesting recent mobility of Helitrons is actively altering the transcriptional response within the C. elegans population. Our studies reveal that Helitrons have co-opted new genes into the HSR in numerous Caenorhabditis species, and provide a striking example of the ability of transposable elements to act as agents of evolution by rewiring transcriptional responses and increasing variation within and among populations.

Chu KW et al. (2002) Aquat Toxicol "Synergistic toxicity of multiple heavy metals is revealed by a biological assay using a nematode and its transgenic derivative."

Chow KL, Chu KW

[Aquat Toxicol, 2002]

Caenorhabditis elegans, a free-living nematode species, was adopted for a toxicity bioassay of 10 heavy metals. The lethal concentration (LC) of these metals was determined. Based on these data, we conducted pairwise and triple metal combination testing and demonstrated that these heavy metals displayed synergistic killing effects on C. elegans larvae. Drastic increases in mortality rate up to 100% could be observed at low metal concentrations. The results illustrate the complexity of toxicity tests in biological systems and show that physical-chemical monitoring of toxicants may underestimate biohazards in environmental samples. We also demonstrate that a transgenic derivative nematode strain, KC136, carrying a heat shock promoter driven gfp reporter gene could be used to reduce the duration of an assay so that the synergistic effects among toxicants could be revealed. This derivative strain allows rapid and frequent monitoring of environmental hazards, which usually requires the handling of a large number samples. Copyright 2002 Elsevier Science B.V.

Artal-Sanz M et al. (2006) J Cell Biol "Lysosomal biogenesis and function is critical for necrotic cell death in Caenorhabditis elegans."

Syntichaki P, Artal-Sanz M, Samara C, Tavernarakis N

[J Cell Biol, 2006]

Necrotic cell death is defined by distinctive morphological characteristics that are displayed by dying cells (Walker, N.I., B.V. Harmon, G.C. Gobe, and J.F. Kerr. 1988. Methods Achiev. Exp. Pathol. 13:18-54). The cellular events that transpire during necrosis to generate these necrotic traits are poorly understood. Recent studies in the nematode Caenorhabditis elegans show that cytoplasmic acidification develops during necrosis and is required for cell death (Syntichaki, P., C. Samara, and N. Tavernarakis. 2005. Curr. Biol. 15:1249-1254). However, the origin of cytoplasmic acidification remains elusive. We show that the alkalization of endosomal and lysosomal compartments ameliorates necrotic cell death triggered by diverse stimuli. In addition, mutations in genes that result in altered lysosomal biogenesis and function markedly affect neuronal necrosis. We used a genetically encoded fluorescent marker to follow lysosome fate during neurodegeneration in vivo. Strikingly, we found that lysosomes fuse and localize exclusively around a swollen nucleus. In the advanced stages of cell death, the nucleus condenses and migrates toward the periphery of the cell, whereas green fluorescent protein-labeled lysosomal membranes fade, indicating lysosomal rupture. Our findings demonstrate a prominent role for lysosomes in cellular destruction during necrotic cell death, which is likely conserved in metazoans.