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

• Published in: Molecular cell Vol. 59; no. 4; pp. 639 - 650
• Main Authors: Labbadia, Johnathan, Morimoto, Richard I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20-08-2015
• Subjects: Adult Stem Cells - physiology; Animals; Caenorhabditis elegans - cytology; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Epigenesis, Genetic; Heat-Shock Response; Histone Demethylases - genetics; Histone Demethylases - metabolism; Histones - metabolism; Promoter Regions, Genetic; Protein Binding; Protein Transport; Reproduction; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2015.06.027

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.
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•Stress responses are rapidly repressed at the onset of egg laying in C. elegans•Transcriptional repression at stress response genes is due to increased H3K27me3•Reduced jmjd-3.1 expression underlies increased H3K27me3 at stress response genes•Repression of stress responses is regulated by germline stem cells
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.