set-26
C. elegans
Histone-lysine N-methyltransferase set-26
What the model saw
Gene: set-26 Organism: Caenorhabditis elegans Known functions: Histone-lysine N-methyltransferase set-26. histone H3K9 methyltransferase activity. histone H3K9 trimethyltransferase activity.
View unredacted entry
Histone-lysine N-methyltransferase set-26. histone H3K9 methyltransferase activity. histone H3K9 trimethyltransferase activity.
Solver output
SET-26 catalyzes histone H3K9 mono/trimethylation, a repressive chromatin mark associated with heterochromatin formation and transcriptional silencing. In C. elegans, H3K9me3 is a hallmark of constitutive heterochromatin and is deposited by SET-domain methyltransferases; loss of this mark has been linked to lifespan extension in multiple studies. Increased H3K9me3 levels promote chromatin compaction and silencing of stress-response and longevity-promoting genes, contributing to epigenetic drift and loss of transcriptional plasticity during aging. Reduction of H3K9 methyltransferase activity (e.g., via met-2 or set-25 loss) extends lifespan in C. elegans, suggesting that the normal function of H3K9 methyltransferases like SET-26 is anti-longevity. The primary mechanism maps to epigenetic alterations, specifically age-associated accumulation of repressive chromatin marks that restrict adaptive gene expression.
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 predicted anti_longevity for set-26. The mechanistic reasoning is sound - H3K9 methyltransferases like SET-26 deposit repressive chromatin marks, and loss of such activity has been linked to lifespan extension in C. elegans. The model appropriately references met-2 and set-25 as analogous H3K9 methyltransferases whose loss extends lifespan. The reasoning is well-grounded in the epigenetic aging literature for C. elegans. Confidence of 0.72 is appropriate given the specificity of the gene. Minor note: the model conflates SET-26 with other H3K9 methyltransferases (met-2, set-25) without direct evidence specific to set-26, but the general reasoning is valid and leads to the correct conclusion.
Raw API responses
solver
{
"reasoning": "SET-26 catalyzes histone H3K9 mono/trimethylation, a repressive chromatin mark associated with heterochromatin formation and transcriptional silencing. In C. elegans, H3K9me3 is a hallmark of constitutive heterochromatin and is deposited by SET-domain methyltransferases; loss of this mark has been linked to lifespan extension in multiple studies. Increased H3K9me3 levels promote chromatin compaction and silencing of stress-response and longevity-promoting genes, contributing to epigenetic drift and loss of transcriptional plasticity during aging. Reduction of H3K9 methyltransferase activity (e.g., via met-2 or set-25 loss) extends lifespan in C. elegans, suggesting that the normal function of H3K9 methyltransferases like SET-26 is anti-longevity. The primary mechanism maps to epigenetic alterations, specifically age-associated accumulation of repressive chromatin marks that restrict adaptive gene expression.",
"confidence": 0.72,
"key_pathways": [
"H3K9 methylation / heterochromatin silencing",
"epigenetic chromatin remodeling",
"transcriptional regulation of stress-response genes"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for set-26. The mechanistic reasoning is sound - H3K9 methyltransferases like SET-26 deposit repressive chromatin marks, and loss of such activity has been linked to lifespan extension in C. elegans. The model appropriately references met-2 and set-25 as analogous H3K9 methyltransferases whose loss extends lifespan. The reasoning is well-grounded in the epigenetic aging literature for C. elegans. Confidence of 0.72 is appropriate given the specificity of the gene. Minor note: the model conflates SET-26 with other H3K9 methyltransferases (met-2, set-25) without direct evidence specific to set-26, but the general reasoning is valid and leads to the correct conclusion.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}