Transcriptional regulation as a dose-dependent process: insights from transcription factor tuning

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,...

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Main Author: Gemma Noviello
Format: Article
Language:English
Published: The Royal Society 2025-08-01
Series:Open Biology
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Online Access:https://royalsocietypublishing.org/doi/10.1098/rsob.240328
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author Gemma Noviello
author_facet Gemma Noviello
author_sort Gemma Noviello
collection DOAJ
description 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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spelling doaj-art-b09cef67ad9e40dfaef6d5ab12fce1ba2025-08-20T02:56:39ZengThe Royal SocietyOpen Biology2046-24412025-08-0115810.1098/rsob.240328Transcriptional regulation as a dose-dependent process: insights from transcription factor tuningGemma Noviello0Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory Rome, Monterotondo, Roma 00015, ItalySeveral 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.https://royalsocietypublishing.org/doi/10.1098/rsob.240328transcription factortuningdose-dependent processbinding sites affinityCRISPRdegron
spellingShingle Gemma Noviello
Transcriptional regulation as a dose-dependent process: insights from transcription factor tuning
Open Biology
transcription factor
tuning
dose-dependent process
binding sites affinity
CRISPR
degron
title Transcriptional regulation as a dose-dependent process: insights from transcription factor tuning
title_full Transcriptional regulation as a dose-dependent process: insights from transcription factor tuning
title_fullStr Transcriptional regulation as a dose-dependent process: insights from transcription factor tuning
title_full_unstemmed Transcriptional regulation as a dose-dependent process: insights from transcription factor tuning
title_short Transcriptional regulation as a dose-dependent process: insights from transcription factor tuning
title_sort transcriptional regulation as a dose dependent process insights from transcription factor tuning
topic transcription factor
tuning
dose-dependent process
binding sites affinity
CRISPR
degron
url https://royalsocietypublishing.org/doi/10.1098/rsob.240328
work_keys_str_mv AT gemmanoviello transcriptionalregulationasadosedependentprocessinsightsfromtranscriptionfactortuning