hht1
S. pombe
histone H3 h3.1
What the model saw
Gene: hht1 Organism: Schizosaccharomyces pombe Known functions: histone H3 h3.1. DNA binding. chromatin-protein adaptor activity. nucleosomal DNA binding. protein binding. protein heterodimerization activity. structural constituent of chromatin.
View unredacted entry
histone H3 h3.1. DNA binding. chromatin-protein adaptor activity. nucleosomal DNA binding. protein binding. protein heterodimerization activity. structural constituent of chromatin.
Solver output
hht1 encodes histone H3.1 in S. pombe, a core structural constituent of chromatin that binds nucleosomal DNA and acts as a chromatin-protein adaptor. Proper histone H3 stoichiometry and chromatin packaging are essential for maintaining epigenetic marks (e.g., H3K4me3, H3K9me3, H3K36me3) that regulate gene silencing, heterochromatin integrity, and transcriptional fidelity. Loss of histone H3 function leads to chromatin decompaction, aberrant transcription, and erosion of epigenetic information — all hallmarks of aging. In yeast models, maintaining correct histone levels and nucleosome occupancy suppresses age-associated transcriptional noise and genomic instability. The chromatin-protein adaptor activity further supports recruitment of silencing complexes (e.g., CLRC/Clr4) at pericentromeric and subtelomeric regions, preserving heterochromatin that is progressively lost during 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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumes that histone H3.1 (hht1) is beneficial for longevity because it maintains chromatin integrity and epigenetic silencing. However, in S. pombe, hht1 is actually anti-longevity, meaning its presence/activity reduces lifespan. This is consistent with findings in yeast where excess histone H3 or specific histone variants can be detrimental — for example, in S. cerevisiae, deletion of histone genes extends chronological or replicative lifespan. The model's mechanistic reasoning is plausible-sounding but leads to the wrong conclusion. The model was moderately confident (0.65) in the wrong direction. The reasoning quality is poor because it failed to consider that histone gene deletions in yeast are often associated with lifespan extension (anti_longevity classification for the gene itself).
Raw API responses
solver
{
"reasoning": "hht1 encodes histone H3.1 in S. pombe, a core structural constituent of chromatin that binds nucleosomal DNA and acts as a chromatin-protein adaptor. Proper histone H3 stoichiometry and chromatin packaging are essential for maintaining epigenetic marks (e.g., H3K4me3, H3K9me3, H3K36me3) that regulate gene silencing, heterochromatin integrity, and transcriptional fidelity. Loss of histone H3 function leads to chromatin decompaction, aberrant transcription, and erosion of epigenetic information — all hallmarks of aging. In yeast models, maintaining correct histone levels and nucleosome occupancy suppresses age-associated transcriptional noise and genomic instability. The chromatin-protein adaptor activity further supports recruitment of silencing complexes (e.g., CLRC/Clr4) at pericentromeric and subtelomeric regions, preserving heterochromatin that is progressively lost during aging.",
"confidence": 0.65,
"key_pathways": [
"histone H3 nucleosome assembly and chromatin compaction",
"heterochromatin silencing via H3K9 methylation (Clr4/CLRC pathway)",
"epigenetic maintenance of transcriptional fidelity"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumes that histone H3.1 (hht1) is beneficial for longevity because it maintains chromatin integrity and epigenetic silencing. However, in S. pombe, hht1 is actually anti-longevity, meaning its presence/activity reduces lifespan. This is consistent with findings in yeast where excess histone H3 or specific histone variants can be detrimental — for example, in S. cerevisiae, deletion of histone genes extends chronological or replicative lifespan. The model's mechanistic reasoning is plausible-sounding but leads to the wrong conclusion. The model was moderately confident (0.65) in the wrong direction. The reasoning quality is poor because it failed to consider that histone gene deletions in yeast are often associated with lifespan extension (anti_longevity classification for the gene itself).",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}