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Transcriptional Regulation as a Dose‐dependent Process: Insights From Transcription Factor Tuning

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Noviello, Gemma·2025·Open Biology
DOI 10.1098/rsob.240328PMC PMC12324873
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Abstract

Several biological processes, including transcriptional regulation by transcription factors (TFs), are dose-dependent. At the mathematical level, dose-dependent processes can be modelled by fitting dose–response curves, for istance, employing Hill-type equations. At the experimental level, however, quantitatively regulating, or tuning, endogenous gene expression to characterize dose-dependent processes is challenging. Here, existing methods to fine-tune endogenous gene expression are compared and contrasted. Relatively small TF dosage variations have been shown to underpin cell fate decisions. Nonetheless, the current understanding of the molecular mechanisms by which TFs quantitatively regulate gene expression is limited, due to the paucity of genome-wide studies in endogenous and physiological conditions. Recent works combining quantitative perturbations of TFs and genome-wide response analyses are untangling an underexplored layer of transcriptional control. At the same time, new questions are emerging in the field, which will require further technological advancements in order to be addressed.

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Authors
Noviello, G.
Affiliations
European Molecular Biology Laboratory (IT)
Corresponding author
Noviello, Gemma
ORCID
Noviello, Gemma
Venue
Open Biology
Publisher
The Royal Society
Published
2025-08
Volume
15
Issue
8
Pages
240328-240328
ISSN
2046-2441 (ISSN-L)
DOI
10.1098/rsob.240328
PMC
PMC12324873
OpenAlex
W4413039817
Cited by
13
References
6
Citations by year
2026: 10 · 2025: 3
FWCI
1.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Open Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
transcriptional regulation, dose-dependent regulation, transcription factor dosage, dose-response curves, cell fate determination, endogenous gene expression
MeSH terms
Animals, Gene Expression Regulation, Humans, Transcription Factors, Transcription, Genetic

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