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.