DAF-12 germline-to-soma signaling mediates transgenerational longevity in <i>C. elegans</i>

<jats:title>ABSTRACT</jats:title> <jats:p> Development requires the complex coordination of gene regulatory networks that must remain robust in the face of variable environmental cues. In <jats:italic>Caenorhabditis elegans</jats:italic> , the nuclear hormone receptor DAF-12 integrates metabolic cues and hormonal signals to control important life history decisions, including development, reproduction, and the rate of aging. Here, we tested the involvement of DAF-12 germline-to-soma signaling in two transgenerational longevity mutants, <jats:italic>wdr-5</jats:italic> and <jats:italic>jhdm-1</jats:italic> . We have previously shown that both mutant populations gradually accumulate repressive H3K9me2 over multiple generations, which is necessary and sufficient for their lifespan extension. We find that <jats:italic>daf-12</jats:italic> activity was required for the epigenetic establishment of longevity in both mutant populations, but was only necessary for maintaining longevity in a <jats:italic>wdr-5</jats:italic> mutant background. Because DAF-12 also functions as a key regulator of dauer diapause, an alternative developmental stage triggered by environmental stress, we also tested the genetic relationship at earlier points in development. Surprisingly, mutations in either <jats:italic>wdr-5</jats:italic> or <jats:italic>jhdm-1</jats:italic> rescued the dauer defect of <jats:italic>daf-12</jats:italic> mutants, and we found a synergistic effect on unchallenged larval development in <jats:italic>wdr-5; daf-12</jats:italic> double mutants. These differing epistatic relationships indicate that, although the acquisition of longevity in both <jats:italic>wdr-5</jats:italic> and <jats:italic>jhdm-1</jats:italic> mutant populations shares a common mechanism, the impacts on somatic phenotypes (including lifespan extension) proceed via distinct pathways. Together, these results show how heritable chromatin states can co-opt existing developmental programs to influence key developmental decisions. </jats:p> <jats:sec> <jats:title>ARTICLE SUMMARY</jats:title> <jats:p> How do early experiences influence development and aging? In this study, we explore this question by testing the genetic interaction between the DAF-12 signaling pathway and heritable chromatin landscapes. Previously, we showed that two <jats:italic>C. elegans</jats:italic> mutants can accumulate heterochromatin over multiple generations to acquire longevity. We find that DAF-12 is required to establish this epigenetic trait but is not necessary to maintain it. We also find that chromatin landscapes bypass DAF-12’s role earlier in development, including during the decision to enter dauer diapause. Overall, this study shows how chromatin states co-opt existing developmental programs to influence key life history decisions. </jats:p> </jats:sec>