SUMMARY Germline development is sensitive to nutrient availability and environmental perturbation. Heat shock transcription factor 1 (HSF1), a key transcription factor driving the cellular heat shock response (HSR), is also involved in gametogenesis. The precise function of HSF1 (HSF-1 in C. elegans ) and its regulation in germline development are poorly understood. Using the auxin-inducible degron system in C. elegans , we uncovered a role of HSF-1 in progenitor cell proliferation and early meiosis and identified a compact but important transcriptional program of HSF-1 in germline development. Interestingly, heat stress only induces the canonical HSR in a subset of germ cells but impairs HSF-1 binding at its developmental targets. Conversely, insulin/insulin growth factor 1 (IGF-1) signaling dictates the requirement for HSF-1 in germline development and functions through repressing FOXO/DAF-16 in the soma to activate HSF-1 in germ cells. We propose that this non-cell-autonomous mechanism couples nutrient-sensing insulin/IGF-1 signaling to HSF-1 activation to support homeostasis in rapid germline growth.

HSF-1 is a key regulator of cellular proteotoxic stress response and is required for animal lifespan. In C. elegans, HSF-1 mediated heat shock response (HSR) declines sharply on the first day of adulthood, and HSF-1 was proposed to function primarily during larval stages for lifespan assurance based on studies using RNAi. The tissue requirement for HSF-1 in lifespan, however, is not well understood. Using the auxin-inducible degron (AID) system, we manage to uncouple the roles of HSF-1 in development and longevity. In wild-type animals, we find HSF-1 is required during the whole self-reproductive period for lifespan. This period is extended in long-lived animals that have arrested germline stem cells (GSC) or reduced insulin/IGF-1 signaling (IIS). While depletion of HSF-1 from any major somatic tissues during development results in severe defects, HSF-1 primarily functions in the intestine and likely neural system of adults to support lifespan. Finally, by combining AID and genome-wide transcriptional analyses, we find HSF-1 directly activates the transcription of constitutively-expressed chaperone and co-chaperone genes among others in early adulthood, which underlies its roles in longevity assurance.

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