hsf-1
C. elegans
Heat shock transcription factor hsf-1
What the model saw
Gene: hsf-1 Organism: Caenorhabditis elegans Known functions: Heat shock transcription factor hsf-1. DNA-binding transcription factor activity. RNA polymerase II cis-regulatory region sequence-specific DNA binding. calmodulin binding. chromatin binding. identical protein binding. promoter-specific chromatin binding. protein binding. sequence-specific DNA binding. sequence-specific double-stranded DNA binding.
View unredacted entry
Heat shock transcription factor hsf-1. DNA-binding transcription factor activity. RNA polymerase II cis-regulatory region sequence-specific DNA binding. calmodulin binding. chromatin binding. identical protein binding. promoter-specific chromatin binding. protein binding. sequence-specific DNA binding. sequence-specific double-stranded DNA binding.
Solver output
HSF-1 is the master heat shock transcription factor in C. elegans that binds heat shock elements (HSEs) in promoters of chaperone genes (e.g., hsp-70, hsp-90, hsp-16 family) via its sequence-specific double-stranded DNA binding activity, driving their transcriptional upregulation. This proteostasis network maintenance is essential for clearing misfolded proteins and preventing toxic aggregation. HSF-1 is a well-established pro-longevity factor in C. elegans: it acts downstream of the DAF-2/insulin-IGF-1 signaling pathway (where DAF-16/FOXO and HSF-1 cooperate to extend lifespan), and hsf-1 overexpression extends lifespan while hsf-1 loss-of-function dramatically shortens it. Its calmodulin binding and chromatin/promoter-specific binding activities further support its role as a regulated transcriptional activator of the proteostasis machinery. The primary mechanism is transcriptional induction of molecular chaperones that maintain protein folding homeostasis throughout aging.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model correctly identified hsf-1 as pro_longevity with high confidence (0.95). The mechanistic reasoning is excellent and accurate: HSF-1 is indeed the master heat shock transcription factor in C. elegans, it does regulate chaperone genes (hsp-70, hsp-90, hsp-16 family), it does act downstream of DAF-2/insulin-IGF-1 signaling in cooperation with DAF-16/FOXO, and hsf-1 overexpression does extend lifespan while loss-of-function shortens it. The model correctly connected the listed molecular functions (sequence-specific DNA binding, chromatin binding, promoter-specific chromatin binding) to its role in transcriptional activation of proteostasis machinery. All key pathways identified are accurate and relevant.
Raw API responses
solver
{
"reasoning": "HSF-1 is the master heat shock transcription factor in C. elegans that binds heat shock elements (HSEs) in promoters of chaperone genes (e.g., hsp-70, hsp-90, hsp-16 family) via its sequence-specific double-stranded DNA binding activity, driving their transcriptional upregulation. This proteostasis network maintenance is essential for clearing misfolded proteins and preventing toxic aggregation. HSF-1 is a well-established pro-longevity factor in C. elegans: it acts downstream of the DAF-2/insulin-IGF-1 signaling pathway (where DAF-16/FOXO and HSF-1 cooperate to extend lifespan), and hsf-1 overexpression extends lifespan while hsf-1 loss-of-function dramatically shortens it. Its calmodulin binding and chromatin/promoter-specific binding activities further support its role as a regulated transcriptional activator of the proteostasis machinery. The primary mechanism is transcriptional induction of molecular chaperones that maintain protein folding homeostasis throughout aging.",
"confidence": 0.95,
"key_pathways": [
"heat shock response / chaperone transcription (HSF-1 → hsp-70/hsp-90)",
"insulin/IGF-1 signaling longevity pathway (DAF-2 → DAF-16/HSF-1)",
"proteostasis network maintenance"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified hsf-1 as pro_longevity with high confidence (0.95). The mechanistic reasoning is excellent and accurate: HSF-1 is indeed the master heat shock transcription factor in C. elegans, it does regulate chaperone genes (hsp-70, hsp-90, hsp-16 family), it does act downstream of DAF-2/insulin-IGF-1 signaling in cooperation with DAF-16/FOXO, and hsf-1 overexpression does extend lifespan while loss-of-function shortens it. The model correctly connected the listed molecular functions (sequence-specific DNA binding, chromatin binding, promoter-specific chromatin binding) to its role in transcriptional activation of proteostasis machinery. All key pathways identified are accurate and relevant.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}