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Record W4414547352 · doi:10.1017/qrd.2025.10013

Thermodynamic control of gene regulation

2025· review· en· W4414547352 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueQRB Discovery · 2025
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDNA and Nucleic Acid Chemistry
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsTranscription (linguistics)GeneRegulation of gene expressionPopulationRNA polymerasePromoterDNARNAContext (archaeology)

Abstract

fetched live from OpenAlex

Abstract G-quadruplexes and i -motifs are non-canonical secondary structures of DNA that act as conformational switches in controlling genomic events. Within the genome, G- and C-rich sequences with the potential to fold into G-quadruplexes and i -motifs are overrepresented in important regulatory domains, including, but not limited to, the promoter regions of oncogenes. We previously have shown that some promoter sequences can adopt coexisting duplex, G-quadruplex, i -motif, and coiled conformations; moreover, their distribution can be modelled as a dynamic equilibrium in which the fractional population of each conformation is determined by the sequence and local conditions. On that basis, we proposed a hypothesis in which the level of expression of a gene with G- and C-rich sequences in the promoter is regulated thermodynamically by fine-tuning the duplex-to-G-quadruplex ratio, with the G-quadruplex modulating RNA polymerase activity. Any deviation from the evolutionarily tuned, gene-specific distribution of conformers, such as might result from mutations in the promoter or a change in cellular conditions, may lead to under- or overexpression of the gene and pathological consequences. We now expand on this hypothesis in the context of supporting evidence from molecular and cellular studies and from biophysico-chemical investigations of oligomeric DNA. Thermodynamic control of transcription implies that G-quadruplex and i -motif structures in the genome form as thermodynamically stable conformers in competition with the duplex conformation. That is in addition to their recognized formation as kinetically trapped, metastable states within domains of single-stranded DNA, such as a transcription bubble or R-loop, that are opened in a prior cellular event.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.976
Threshold uncertainty score0.865

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.007
GPT teacher head0.262
Teacher spread0.255 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it