his-71
C. elegans
Histone H3.3 type 1
What the model saw
Gene: his-71 Organism: Caenorhabditis elegans Known functions: Histone H3.3 type 1. DNA binding. nucleosomal DNA binding. protein heterodimerization activity. structural constituent of chromatin.
View unredacted entry
Histone H3.3 type 1. DNA binding. nucleosomal DNA binding. protein heterodimerization activity. structural constituent of chromatin.
Solver output
his-71 encodes a Histone H3.3 variant, a replication-independent histone that is specifically deposited at actively transcribed genes, enhancers, and telomeres, playing a critical role in maintaining chromatin integrity and epigenetic memory. As a structural constituent of chromatin with nucleosomal DNA binding activity, H3.3 helps preserve proper chromatin architecture and gene expression patterns that erode with age. In C. elegans, histone H3.3 incorporation is essential for maintaining epigenetic states at key longevity-associated loci, including those regulated by the DAF-16/FOXO and germline pathways. Loss of H3.3 leads to chromatin instability, aberrant gene expression, and accelerated epigenetic drift—hallmarks of aging. The protein heterodimerization activity reflects its assembly into H3.3-H4 dimers required for nucleosome formation, supporting stable chromatin compaction that counteracts age-associated epigenetic dysregulation.
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 his-71 (Histone H3.3). The mechanistic reasoning is plausible and generally sound — H3.3 as a replication-independent histone involved in epigenetic maintenance is a reasonable framework. However, some specifics (e.g., DAF-16/FOXO connection, specific C. elegans H3.3 studies) appear to be inferred/extrapolated rather than directly evidenced, which slightly reduces confidence in the mechanistic accuracy. The core logic (chromatin integrity → longevity) is appropriate. Confidence of 0.62 is reasonable given the indirect nature of the evidence.
Raw API responses
solver
{
"reasoning": "his-71 encodes a Histone H3.3 variant, a replication-independent histone that is specifically deposited at actively transcribed genes, enhancers, and telomeres, playing a critical role in maintaining chromatin integrity and epigenetic memory. As a structural constituent of chromatin with nucleosomal DNA binding activity, H3.3 helps preserve proper chromatin architecture and gene expression patterns that erode with age. In C. elegans, histone H3.3 incorporation is essential for maintaining epigenetic states at key longevity-associated loci, including those regulated by the DAF-16/FOXO and germline pathways. Loss of H3.3 leads to chromatin instability, aberrant gene expression, and accelerated epigenetic drift—hallmarks of aging. The protein heterodimerization activity reflects its assembly into H3.3-H4 dimers required for nucleosome formation, supporting stable chromatin compaction that counteracts age-associated epigenetic dysregulation.",
"confidence": 0.62,
"key_pathways": [
"Histone H3.3 chromatin deposition and epigenetic maintenance",
"Nucleosome assembly and chromatin integrity",
"DAF-16/FOXO-associated transcriptional regulation"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for his-71 (Histone H3.3). The mechanistic reasoning is plausible and generally sound — H3.3 as a replication-independent histone involved in epigenetic maintenance is a reasonable framework. However, some specifics (e.g., DAF-16/FOXO connection, specific C. elegans H3.3 studies) appear to be inferred/extrapolated rather than directly evidenced, which slightly reduces confidence in the mechanistic accuracy. The core logic (chromatin integrity → longevity) is appropriate. Confidence of 0.62 is reasonable given the indirect nature of the evidence.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}