utx-1
C. elegans
JmjC domain-containing protein
What the model saw
Gene: utx-1 Organism: Caenorhabditis elegans Known functions: JmjC domain-containing protein. RNA polymerase II cis-regulatory region sequence-specific DNA binding. chromatin DNA binding. histone H3K27me2/H3K27me3 demethylase activity. histone demethylase activity.
View unredacted entry
JmjC domain-containing protein. RNA polymerase II cis-regulatory region sequence-specific DNA binding. chromatin DNA binding. histone H3K27me2/H3K27me3 demethylase activity. histone demethylase activity.
Solver output
UTX-1 is a JmjC domain-containing histone demethylase that specifically removes the repressive H3K27me2/me3 marks from chromatin. H3K27me3 is deposited by the PRC2 complex and is associated with transcriptional silencing of genes; its removal by UTX-1 activates gene expression. In C. elegans, H3K27me3 levels increase with age and are maintained by the PRC2 complex, which has been shown to promote longevity by silencing pro-aging gene programs. Loss of utx-1 (demethylase) leads to increased H3K27me3 and extended lifespan, while overactivity of UTX-1 reduces H3K27me3 levels and shortens lifespan. Thus, the normal demethylase function of UTX-1 opposes longevity by erasing a protective repressive epigenetic mark, effectively de-repressing pro-aging transcriptional programs.
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 utx-1 as anti_longevity with high confidence (0.88). The mechanistic reasoning is excellent and accurate: UTX-1 is a H3K27me2/me3 demethylase, H3K27me3 is a repressive mark that increases with age and promotes longevity in C. elegans, loss of utx-1 leads to increased H3K27me3 and extended lifespan, while UTX-1 activity opposes longevity by erasing this protective epigenetic mark. The model correctly identifies the PRC2-H3K27me3 pathway and the role of epigenetic silencing in longevity. The reasoning is mechanistically sound and well-supported by the literature on C. elegans aging.
Raw API responses
solver
{
"reasoning": "UTX-1 is a JmjC domain-containing histone demethylase that specifically removes the repressive H3K27me2/me3 marks from chromatin. H3K27me3 is deposited by the PRC2 complex and is associated with transcriptional silencing of genes; its removal by UTX-1 activates gene expression. In C. elegans, H3K27me3 levels increase with age and are maintained by the PRC2 complex, which has been shown to promote longevity by silencing pro-aging gene programs. Loss of utx-1 (demethylase) leads to increased H3K27me3 and extended lifespan, while overactivity of UTX-1 reduces H3K27me3 levels and shortens lifespan. Thus, the normal demethylase function of UTX-1 opposes longevity by erasing a protective repressive epigenetic mark, effectively de-repressing pro-aging transcriptional programs.",
"confidence": 0.88,
"key_pathways": [
"H3K27me3 demethylation via JmjC domain",
"PRC2-H3K27me3 epigenetic silencing pathway",
"RNA Pol II transcriptional activation"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted utx-1 as anti_longevity with high confidence (0.88). The mechanistic reasoning is excellent and accurate: UTX-1 is a H3K27me2/me3 demethylase, H3K27me3 is a repressive mark that increases with age and promotes longevity in C. elegans, loss of utx-1 leads to increased H3K27me3 and extended lifespan, while UTX-1 activity opposes longevity by erasing this protective epigenetic mark. The model correctly identifies the PRC2-H3K27me3 pathway and the role of epigenetic silencing in longevity. The reasoning is mechanistically sound and well-supported by the literature on C. elegans aging.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}