Abstract
The heat shock response (HSR) is essential for proteostasis and cellular health. In metazoans, aging is associated with a decline in quality control, thus increasing the risk for protein conformational disease. Here, we show that in C. elegans, the HSR declines precipitously over a 4 hr period in early adulthood coincident with the onset of reproductive maturity. Repression of the HSR occurs due to an increase in H3K27me3 marks at stress gene loci, the timing of which is determined by reduced expression of the H3K27 demethylase jmjd-3.1. This results in a repressed chromatin state that interferes with HSF-1 binding and suppresses transcription initiation in response to stress. The removal of germline stem cells preserves jmjd-3.1 expression, suppresses the accumulation of H3K27me3 at stress gene loci, and maintains the HSR. These findings suggest that competing requirements of the germline and soma dictate organismal stress resistance as animals begin reproduction. It is thought that the progressive dysregulation of stress response pathways contributes to aging in metazoans. Here, Labbadia and Morimoto demonstrate that stress responses are rapidly repressed early in C. elegans adulthood as part of a genetically programmed event controlled by germ line stem cells through alterations in chromatin accessibility.
Original language | English (US) |
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Pages (from-to) | 639-650 |
Number of pages | 12 |
Journal | Molecular cell |
Volume | 59 |
Issue number | 4 |
DOIs | |
State | Published - Aug 20 2015 |
Funding
These studies were supported by a Postdoctoral Fellowship to J.L. from the ALS Association and grants from the National Institutes of Health (NIGMS, NIA, NIMH), the Ellison Medical Foundation, and the Daniel F. and Ada L. Rice Foundation to R.I.M. The authors thank the members of the R.I.M. Laboratory for their support and critical reading of the manuscript. We also thank Steven Zuryn and Sophie Jairrault for jmjd-3.1 over-expression line IS1427and IS1572, the Lithgow lab (Buck institute) for anti HSP-16.2 antibody, Netta Shemesh and Anat Ben-Zvi (Ben Gurion University) for gon-2 and glp-4 worm strains, and the Northwestern University Biological Imaging Facility and Keck biophysics facilities for instrument use.
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology