Article Gene bookmarking by the heat shock transcription factor programs the insulin-like signaling pathway
Maternal stress can have long-lasting epigenetic effects on offspring. To examine how epigenetic changes
are triggered by stress, we examined the effects of activating the universal stress-responsive heat shock
transcription factor HSF-1 in the germline of Caenorhabditis elegans. We show that, when activated in
germ cells, HSF-1 recruits MET-2, the putative histone 3 lysine 9 (H3K9) methyltransferase responsible for
repressive H3K9me2 (H3K9 dimethyl) marks in chromatin, and negatively bookmarks the insulin receptor
daf-2 and other HSF-1 target genes. Increased H3K9me2 at these genes persists in adult progeny and shifts
their stress response strategy away from inducible chaperone expression as a mechanism to survive stress
and instead rely on decreased insulin/insulin growth factor (IGF-1)-like signaling (IIS). Depending on the dura-
tion of maternal heat stress exposure, this epigenetic memory is inherited by the next generation. Thus, para-
doxically, HSF-1 recruits the germline machinery normally responsible for erasing transcriptional memory
but, instead, establishes a heritable epigenetic memory of prior stress exposure.
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