CHD1

S. cerevisiae

chromatin-remodeling ATPase CHD1

What the model saw

Gene: CHD1
Organism: Saccharomyces cerevisiae
Known functions: chromatin-remodeling ATPase CHD1. ATP binding. ATP hydrolysis activity. ATP-dependent activity, acting on DNA. ATP-dependent chromatin remodeler activity. DNA binding. chromatin DNA binding. chromatin binding. histone H3K4me3 reader activity. histone binding. nucleosome array spacer activity. rDNA binding. transcription cis-regulatory region binding.

View unredacted entry

chromatin-remodeling ATPase CHD1. ATP binding. ATP hydrolysis activity. ATP-dependent activity, acting on DNA. ATP-dependent chromatin remodeler activity. DNA binding. chromatin DNA binding. chromatin binding. histone H3K4me3 reader activity. histone binding. nucleosome array spacer activity. rDNA binding. transcription cis-regulatory region binding.

Solver output

Predicted influence

Pro-longevity

Confidence

72%

Mechanism

Epigenetic alterations

Reasoning

CHD1 is an ATP-dependent chromatin remodeler that reads the H3K4me3 active transcription mark and spaces nucleosome arrays, maintaining proper chromatin architecture at actively transcribed genes. Its rDNA binding activity is particularly relevant to yeast aging: rDNA stability is a central determinant of replicative lifespan in S. cerevisiae, and proper nucleosome positioning at rDNA suppresses extrachromosomal rDNA circle (ERC) formation, a key driver of yeast aging. By organizing nucleosomes at rDNA loci and coupling H3K4me3 recognition to transcriptional fidelity, CHD1 helps preserve epigenome integrity and genomic stability at repetitive loci. Loss of CHD1 function leads to nucleosome disorganization, increased rDNA instability, and dysregulated transcription, all of which are associated with shortened replicative lifespan. Thus, CHD1's normal function in maintaining ordered chromatin and rDNA integrity is expected to be pro-longevity.

Key pathways

rDNA chromatin organization and ERC suppressionH3K4me3-coupled nucleosome remodelingATP-dependent nucleosome spacing

Longevity influence

Anti-longevity

Lifespan effect

Increase and Decrease

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

Answer

✗Incorrect

Mechanism

✗Incorrect

Reasoning quality

2/5

Failure mode

Confident wrong

Notes

The model predicted CHD1 as pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning about rDNA stability and ERC suppression sounds plausible on the surface, but it led to the wrong conclusion. In yeast, CHD1 deletion actually extends lifespan, making it anti_longevity (i.e., its normal function shortens life). The model's mechanistic reasoning was inverted - it assumed CHD1 promotes longevity by maintaining rDNA stability, but the actual finding is that CHD1 activity is detrimental to lifespan. The model was fairly confident (0.72) in its wrong answer, and the mechanistic reasoning, while internally coherent, does not match the empirical data from GenAge.

Raw API responses

solver

{
  "reasoning": "CHD1 is an ATP-dependent chromatin remodeler that reads the H3K4me3 active transcription mark and spaces nucleosome arrays, maintaining proper chromatin architecture at actively transcribed genes. Its rDNA binding activity is particularly relevant to yeast aging: rDNA stability is a central determinant of replicative lifespan in S. cerevisiae, and proper nucleosome positioning at rDNA suppresses extrachromosomal rDNA circle (ERC) formation, a key driver of yeast aging. By organizing nucleosomes at rDNA loci and coupling H3K4me3 recognition to transcriptional fidelity, CHD1 helps preserve epigenome integrity and genomic stability at repetitive loci. Loss of CHD1 function leads to nucleosome disorganization, increased rDNA instability, and dysregulated transcription, all of which are associated with shortened replicative lifespan. Thus, CHD1's normal function in maintaining ordered chromatin and rDNA integrity is expected to be pro-longevity.",
  "confidence": 0.72,
  "key_pathways": [
    "rDNA chromatin organization and ERC suppression",
    "H3K4me3-coupled nucleosome remodeling",
    "ATP-dependent nucleosome spacing"
  ],
  "mechanism_class": "epigenetic_alterations",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model predicted CHD1 as pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning about rDNA stability and ERC suppression sounds plausible on the surface, but it led to the wrong conclusion. In yeast, CHD1 deletion actually extends lifespan, making it anti_longevity (i.e., its normal function shortens life). The model's mechanistic reasoning was inverted - it assumed CHD1 promotes longevity by maintaining rDNA stability, but the actual finding is that CHD1 activity is detrimental to lifespan. The model was fairly confident (0.72) in its wrong answer, and the mechanistic reasoning, while internally coherent, does not match the empirical data from GenAge.",
  "failure_mode": "confident_wrong",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}