Repression of the Heat Shock Response Is a Programmed Event at the Onset of Reproduction

Johnathan Labbadia, Richard I. Morimoto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

152 Scopus citations

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 languageEnglish (US)
Pages (from-to)639-650
Number of pages12
JournalMolecular cell
Volume59
Issue number4
DOIs
StatePublished - Aug 20 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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