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Record W4414547352 · doi:10.1017/qrd.2025.10013

Thermodynamic control of gene regulation

2025· review· en· W4414547352 on OpenAlexaff
James W. Wells, Tigran V. Chalikian

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designTheoretical or conceptual
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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