Diversification of the Caenorhabditis heat shock response by Helitron transposable elements

  1. Jacob M Garrigues
  2. Brian V Tsu
  3. Matthew D Daugherty
  4. Amy E Pasquinelli  Is a corresponding author
  1. University of California, San Diego, United States

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.

Data availability

The RNA-seq datasets generated in this study are available at the Gene Expression Omnibus (GEO) under accession number GSE135987.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Jacob M Garrigues

    Division of Biology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Brian V Tsu

    Division of Biology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Matthew D Daugherty

    Division of Biology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4879-9603
  4. Amy E Pasquinelli

    Division of Biology, University of California, San Diego, La Jolla, United States
    For correspondence
    apasquinelli@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9511-0039

Funding

National Institute of General Medical Sciences (R35 GM127012)

  • Amy E Pasquinelli

National Institute of General Medical Sciences (GM133633)

  • Matthew D Daugherty

National Cancer Institute (T32 CA009523)

  • Jacob M Garrigues

National Institute of General Medical Sciences (T32 GM007240)

  • Brian V Tsu

Pew Charitable Trusts

  • Matthew D Daugherty

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2019, Garrigues et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,654
    views
  • 332
    downloads
  • 26
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Jacob M Garrigues
  2. Brian V Tsu
  3. Matthew D Daugherty
  4. Amy E Pasquinelli
(2019)
Diversification of the Caenorhabditis heat shock response by Helitron transposable elements
eLife 8:e51139.
https://doi.org/10.7554/eLife.51139

Share this article

https://doi.org/10.7554/eLife.51139

Further reading

    1. Genetics and Genomics
    Shaohua Gu, Yuanzhe Shao ... Zhiyuan Li
    Research Article

    Microbial secondary metabolites are a rich source for pharmaceutical discoveries and play crucial ecological functions. While tools exist to identify secondary metabolite clusters in genomes, precise sequence-to-function mapping remains challenging because neither function nor substrate specificity of biosynthesis enzymes can accurately be predicted. Here, we developed a knowledge-guided bioinformatic pipeline to solve these issues. We analyzed 1928 genomes of Pseudomonas bacteria and focused on iron-scavenging pyoverdines as model metabolites. Our pipeline predicted 188 chemically different pyoverdines with nearly 100% structural accuracy and the presence of 94 distinct receptor groups required for the uptake of iron-loaded pyoverdines. Our pipeline unveils an enormous yet overlooked diversity of siderophores (151 new structures) and receptors (91 new groups). Our approach, combining feature sequence with phylogenetic approaches, is extendable to other metabolites and microbial genera, and thus emerges as powerful tool to reconstruct bacterial secondary metabolism pathways based on sequence data.

    1. Cancer Biology
    2. Genetics and Genomics
    Joakim W Karlsson, Vasu R Sah ... Jonas A Nilsson
    Research Article

    Uveal melanoma (UM) is a rare melanoma originating in the eye’s uvea, with 50% of patients experiencing metastasis predominantly in the liver. In contrast to cutaneous melanoma, there is only a limited effectiveness of combined immune checkpoint therapies, and half of patients with uveal melanoma metastases succumb to disease within 2 years. This study aimed to provide a path toward enhancing immunotherapy efficacy by identifying and functionally validating tumor-reactive T cells in liver metastases of patients with UM. We employed single-cell RNA-seq of biopsies and tumor-infiltrating lymphocytes (TILs) to identify potential tumor-reactive T cells. Patient-derived xenograft (PDX) models of UM metastases were created from patients, and tumor sphere cultures were generated from these models for co-culture with autologous or MART1-specific HLA-matched allogenic TILs. Activated T cells were subjected to TCR-seq, and the TCRs were matched to those found in single-cell sequencing data from biopsies, expanded TILs, and in livers or spleens of PDX models injected with TILs. Our findings revealed that tumor-reactive T cells resided not only among activated and exhausted subsets of T cells, but also in a subset of cytotoxic effector cells. In conclusion, combining single-cell sequencing and functional analysis provides valuable insights into which T cells in UM may be useful for cell therapy amplification and marker selection.