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Record W4406599369 · doi:10.1101/2025.01.19.633652

Gene syntax defines supercoiling-mediated transcriptional feedback

2025· preprint· en· W4406599369 on OpenAlexafffund
Christopher P. Johnstone, Kasey S. Love, Sneha R Kabaria, Ross D. Jones, Albert Blanch-Asensio, Deon S. Ploessl, Emma L. Peterman, Rachel Lee, Jiyoung Yun, Conrad Oakes, Christine L. Mummery, Richard P. Davis, Brandon J. DeKosky, Peter W. Zandstra, Kate E. Galloway

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCRISPR and Genetic Engineering
Canadian institutionsUniversity of British ColumbiaCanada's Michael Smith Genome Sciences CentreUniversity of British Columbia Hospital
FundersNational Science Foundation Graduate Research Fellowship ProgramAir Force Research LaboratoryArmy Research OfficeNational Science FoundationCanadian Institutes of Health ResearchNovo Nordisk FondenNovo NordiskNational Institute of General Medical SciencesInstitute for Collaborative BiotechnologiesMultidisciplinary University Research InitiativeStem Cell NetworkKoch Institute for Integrative Cancer Research, Massachusetts Institute of TechnologyMichael Smith Health Research BCNational Cancer InstituteNational Institutes of Health
KeywordsDNA supercoilGene regulatory networkChromatinBiologyGeneComputational biologyRegulation of gene expressionEnhancerTranscription (linguistics)Gene expressionGenetics

Abstract

fetched live from OpenAlex

Gene syntax-the order and arrangement of genes and their regulatory elements-shapes the dynamic coordination of both natural and synthetic gene circuits. Transcription at one locus profoundly impacts the transcription of nearby adjacent genes, but the molecular basis of this effect remains poorly understood. Here, using integrated reporter circuits in human cells, we show that supercoiling-mediated feedback regulates expression of adjacent genes in a syntax-specific manner. Using Region Capture Micro-C, we measure induction-dependent formation of supercoiled plectonemes and syntax-specific chromatin structures in human induced pluripotent stem cells. Using syntax as a design parameter, we built compact gene circuits, tuning the mean, variance, and stoichiometries of expression across diverse delivery methods and cell types. Integrating supercoiling-mediated feedback into models of gene regulation will expand our understanding of native systems and enhance the design of synthetic gene circuits.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.009
GPT teacher head0.236
Teacher spread0.227 · 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 designBench or experimental
Domainnot available
GenreEmpirical

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

Citations5
Published2025
Admission routes2
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicCRISPR and Genetic EngineeringFrench-language works237,207