Stress resets ancestral heritable small RNA responses
- Tel Aviv University, Israel
Abstract
Transgenerational inheritance of small RNAs challenges basic concepts of heredity. In C. elegans nematodes, small RNAs are transmitted across generations to establish a transgenerational memory trace of ancestral environments and distinguish self-genes from non-self-elements. Carryover of aberrant heritable small RNA responses was shown to be maladaptive and to lead to sterility. Here we show that various types of stress (starvation, high temperatures, and high osmolarity) induce resetting of ancestral small RNA responses and a genome-wide reduction in heritable small RNA levels. We found that mutants that are defective in various stress pathways exhibit irregular RNAi inheritance dynamics even in the absence of stress. Moreover, we discovered that resetting of ancestral RNAi responses is specifically orchestrated by factors that function in the p38 MAPK pathway and the transcription factor SKN-1/Nrf2. Stress-dependent termination of small RNA inheritance could protect from run-on of environment-irrelevant heritable gene regulation.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE129988
-
Stress Resets Transgenerational Small RNA InheritanceNCBI Gene Expression Omnibus, GSE129988.
Article and author information
Author details
Funding
Clore Foundation (Graduate Student Fellowship)
- Leah Houri Zeevi
Milner Foundation (Graduate Student Fellowship)
- Guy Teichman
European Research Council (#335624)
- Oded Rechavi
Israel Science Foundation (#1339/17)
- Oded Rechavi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Kevin Struhl, Harvard Medical School, United States
Version history
- Received: December 30, 2020
- Accepted: March 15, 2021
- Accepted Manuscript published: March 17, 2021 (version 1)
- Version of Record published: April 4, 2021 (version 2)
Copyright
© 2021, Houri Zeevi 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
-
- 5,370
- Page views
-
- 554
- Downloads
-
- 11
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
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)
Stress resets ancestral heritable small RNA responses
eLife 10:e65797.
https://doi.org/10.7554/eLife.65797
Further reading
-
- Chromosomes and Gene Expression
- Genetics and Genomics
Spermatogenesis in the Drosophila male germline proceeds through a unique transcriptional program controlled both by germline-specific transcription factors and by testis-specific versions of core transcriptional machinery. This program includes the activation of genes on the heterochromatic Y chromosome, and reduced transcription from the X chromosome, but how expression from these sex chromosomes is regulated has not been defined. To resolve this, we profiled active chromatin features in the testes from wildtype and meiotic arrest mutants and integrate this with single-cell gene expression data from the Fly Cell Atlas. These data assign the timing of promoter activation for genes with germline-enriched expression throughout spermatogenesis, and general alterations of promoter regulation in germline cells. By profiling both active RNA polymerase II and histone modifications in isolated spermatocytes, we detail widespread patterns associated with regulation of the sex chromosomes. Our results demonstrate that the X chromosome is not enriched for silencing histone modifications, implying that sex chromosome inactivation does not occur in the Drosophila male germline. Instead, a lack of dosage compensation in spermatocytes accounts for the reduced expression from this chromosome. Finally, profiling uncovers dramatic ubiquitinylation of histone H2A and lysine-16 acetylation of histone H4 across the Y chromosome in spermatocytes that may contribute to the activation of this heterochromatic chromosome.
-
- Chromosomes and Gene Expression
- Developmental Biology
Imaging experiments reveal the complex and dynamic nature of the transcriptional hubs associated with Notch signaling.
