jmjd-2
C. elegans
Lysine-specific demethylase 4
What the model saw
Gene: jmjd-2 Organism: Caenorhabditis elegans Known functions: Lysine-specific demethylase 4. histone H3K36 demethylase activity. histone H3K36me/H3K36me2 demethylase activity. histone H3K36me2/H3K36me3 demethylase activity. histone H3K9 demethylase activity. histone H3K9me2/H3K9me3 demethylase activity.
View unredacted entry
Lysine-specific demethylase 4. histone H3K36 demethylase activity. histone H3K36me/H3K36me2 demethylase activity. histone H3K36me2/H3K36me3 demethylase activity. histone H3K9 demethylase activity. histone H3K9me2/H3K9me3 demethylase activity.
Solver output
JMJD-2 is a KDM4-family histone demethylase that removes methyl marks from H3K9me2/me3 and H3K36me2/me3. H3K9me3 is a repressive chromatin mark critical for heterochromatin maintenance and silencing of repetitive elements; its loss through demethylation by JMJD-2 destabilizes constitutive heterochromatin, promoting genomic instability and derepression of transposons — both hallmarks of aging. Additionally, H3K9me3 is required for proper gene silencing during aging in C. elegans, and its maintenance is associated with longevity (e.g., in daf-2 mutants). By demethylating H3K36me2/me3, JMJD-2 also opposes transcriptional fidelity and chromatin compaction. Loss-of-function of KDM4 orthologs has been linked to lifespan extension in C. elegans, consistent with the normal function of jmjd-2 being anti-longevity through erosion of repressive chromatin marks.
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 jmjd-2 in C. elegans with good confidence (0.72). The mechanistic reasoning is sound: JMJD-2 as a KDM4-family demethylase removes H3K9me2/me3 marks, which are repressive chromatin marks important for heterochromatin maintenance. Loss of jmjd-2 would preserve these marks and extend lifespan, making jmjd-2 anti-longevity in its normal function. The reasoning about H3K9me3 heterochromatin maintenance, genomic stability, and transposon silencing during aging is well-grounded in the literature. The model also correctly notes that KDM4 ortholog loss-of-function has been linked to lifespan extension in C. elegans. Minor deduction: the reasoning could be slightly more precise about the specific experimental evidence for jmjd-2 specifically vs. general KDM4 family reasoning, but overall the mechanistic logic is coherent and correct.
Raw API responses
solver
{
"reasoning": "JMJD-2 is a KDM4-family histone demethylase that removes methyl marks from H3K9me2/me3 and H3K36me2/me3. H3K9me3 is a repressive chromatin mark critical for heterochromatin maintenance and silencing of repetitive elements; its loss through demethylation by JMJD-2 destabilizes constitutive heterochromatin, promoting genomic instability and derepression of transposons — both hallmarks of aging. Additionally, H3K9me3 is required for proper gene silencing during aging in C. elegans, and its maintenance is associated with longevity (e.g., in daf-2 mutants). By demethylating H3K36me2/me3, JMJD-2 also opposes transcriptional fidelity and chromatin compaction. Loss-of-function of KDM4 orthologs has been linked to lifespan extension in C. elegans, consistent with the normal function of jmjd-2 being anti-longevity through erosion of repressive chromatin marks.",
"confidence": 0.72,
"key_pathways": [
"H3K9me3 heterochromatin maintenance",
"H3K36 methylation and transcriptional regulation",
"epigenetic reprogramming during aging"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for jmjd-2 in C. elegans with good confidence (0.72). The mechanistic reasoning is sound: JMJD-2 as a KDM4-family demethylase removes H3K9me2/me3 marks, which are repressive chromatin marks important for heterochromatin maintenance. Loss of jmjd-2 would preserve these marks and extend lifespan, making jmjd-2 anti-longevity in its normal function. The reasoning about H3K9me3 heterochromatin maintenance, genomic stability, and transposon silencing during aging is well-grounded in the literature. The model also correctly notes that KDM4 ortholog loss-of-function has been linked to lifespan extension in C. elegans. Minor deduction: the reasoning could be slightly more precise about the specific experimental evidence for jmjd-2 specifically vs. general KDM4 family reasoning, but overall the mechanistic logic is coherent and correct.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}