Diversification of the Caenorhabditis heat shock response by Helitron transposable elements

Jacob M Garrigues,Matthew D Daugherty,Brian V Tsu,Amy E Pasquinelli

doi:10.7554/elife.51139

Abstract

Heat Shock Factor 1 (HSF-1) is a key regulator of the heat shock response (HSR). Upon heat shock, HSF-1 binds well-conserved motifs, called Heat Shock Elements (HSEs), and drives expression of genes important for cellular protection during this stress. Remarkably, we found that substantial numbers of HSEs in multiple Caenorhabditis species reside within Helitrons, a type of DNA transposon. Consistent with Helitron-embedded HSEs being functional, upon heat shock they display increased HSF-1 and RNA polymerase II occupancy and up-regulation of nearby genes in C. elegans. Interestingly, we found that different genes appear to be incorporated into the HSR by species-specific Helitron insertions in C. elegans and C. briggsae and by strain-specific insertions among different wild isolates of C. elegans. Our studies uncover previously unidentified targets of HSF-1 and show that Helitron insertions are responsible for rewiring and diversifying the Caenorhabditis HSR.

Highlights

Heat Shock Factor 1 (HSF-1) is a highly conserved transcription factor that serves as a key regulator of the heat shock response (HSR) (Vihervaara et al, 2018)
Unlike evolutionarily conserved and canonical HSR target genes, we found that Helitron-acquired heat shock elements (HSEs) (Hac-HSEs) control expression of specific G proteincoupled receptor (GPCR) and collagen genes, revealing numerous previously unidentified HSF-1 targets in C. elegans
To determine if other types of Helitrons associate with HSF-1 under non-heat shock (NHS) and heat shock (HS) conditions, publicly available HSF-1 ChIP-seq data (Li et al, 2016) were mapped to the C. elegans genome allowing for mapping to, but preventing pileup at, repetitive regions

Summary

Introduction

Heat Shock Factor 1 (HSF-1) is a highly conserved transcription factor that serves as a key regulator of the heat shock response (HSR) (Vihervaara et al, 2018). Due to the central role HSF-1 has in launching the HSR, much work has been done to determine direct HSF-1 targets by identifying associated genes under different conditions (Gonsalves et al, 2011; Guertin and Lis, 2010; Li et al, 2016; Mahat et al, 2016; Mendillo et al, 2012; Solıs et al, 2016) Most of these studies have focused on HSF-1 binding sites that do not overlap with repetitive sequences such as transposons, potentially leaving a large gap in our understanding of the types of genes that are part of the HSR. While Helitrons were initially discovered in plants and C. elegans (Kapitonov and Jurka, 2001), they have since been identified in a diverse range of species, including humans (Kojima, 2018; Thomas and Pritham, 2015)

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