met-2
C. elegans
Histone-lysine N-methyltransferase met-2
What the model saw
Gene: met-2 Organism: Caenorhabditis elegans Known functions: Histone-lysine N-methyltransferase met-2. DNA binding. histone H3K36 methyltransferase activity. histone H3K9 methyltransferase activity. histone H3K9 monomethyltransferase activity. histone methyltransferase activity. zinc ion binding.
View unredacted entry
Histone-lysine N-methyltransferase met-2. DNA binding. histone H3K36 methyltransferase activity. histone H3K9 methyltransferase activity. histone H3K9 monomethyltransferase activity. histone methyltransferase activity. zinc ion binding.
Solver output
MET-2 is the primary H3K9 mono- and dimethyltransferase in C. elegans (ortholog of mammalian SETDB1/EHMT2), responsible for depositing the repressive H3K9me1/me2 marks that establish constitutive heterochromatin. Loss of H3K9 methylation leads to derepression of transposable elements and repetitive sequences, causing genomic instability and sterility, particularly in the germline. Maintenance of H3K9 methylation-based heterochromatin is critical for silencing transposons and preserving genome integrity across generations, and studies in C. elegans have shown that met-2 loss shortens lifespan and disrupts transgenerational epigenetic inheritance. The H3K9me marks deposited by MET-2 also contribute to proper chromatin compaction during aging, and their progressive loss is a hallmark of epigenetic drift in aging organisms. Thus, MET-2's normal function in maintaining repressive chromatin states supports longevity by preserving epigenomic stability.
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 pro_longevity for met-2 in C. elegans. The mechanistic reasoning is solid and well-grounded: MET-2 as the primary H3K9 methyltransferase (SETDB1/EHMT2 ortholog), its role in heterochromatin formation, transposon silencing, and genome integrity are all accurate. The model correctly notes that met-2 loss shortens lifespan. The reasoning about transgenerational epigenetic inheritance is also relevant. The confidence of 0.72 is appropriate given the complexity of the topic. Minor note: the model mentions H3K36 methyltransferase activity (listed in the entry) but focuses primarily on H3K9 methylation, which is the more relevant activity for longevity. Overall, this is a well-reasoned and correct prediction.
Raw API responses
solver
{
"reasoning": "MET-2 is the primary H3K9 mono- and dimethyltransferase in C. elegans (ortholog of mammalian SETDB1/EHMT2), responsible for depositing the repressive H3K9me1/me2 marks that establish constitutive heterochromatin. Loss of H3K9 methylation leads to derepression of transposable elements and repetitive sequences, causing genomic instability and sterility, particularly in the germline. Maintenance of H3K9 methylation-based heterochromatin is critical for silencing transposons and preserving genome integrity across generations, and studies in C. elegans have shown that met-2 loss shortens lifespan and disrupts transgenerational epigenetic inheritance. The H3K9me marks deposited by MET-2 also contribute to proper chromatin compaction during aging, and their progressive loss is a hallmark of epigenetic drift in aging organisms. Thus, MET-2's normal function in maintaining repressive chromatin states supports longevity by preserving epigenomic stability.",
"confidence": 0.72,
"key_pathways": [
"H3K9 methylation / heterochromatin formation",
"transposable element silencing",
"transgenerational epigenetic inheritance"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for met-2 in C. elegans. The mechanistic reasoning is solid and well-grounded: MET-2 as the primary H3K9 methyltransferase (SETDB1/EHMT2 ortholog), its role in heterochromatin formation, transposon silencing, and genome integrity are all accurate. The model correctly notes that met-2 loss shortens lifespan. The reasoning about transgenerational epigenetic inheritance is also relevant. The confidence of 0.72 is appropriate given the complexity of the topic. Minor note: the model mentions H3K36 methyltransferase activity (listed in the entry) but focuses primarily on H3K9 methylation, which is the more relevant activity for longevity. Overall, this is a well-reasoned and correct prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}