Noviello Gemma
Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory Rome, Monterotondo, Roma 00015, Italy.
Open Biol. 2025 Aug;15(8):240328. doi: 10.1098/rsob.240328. Epub 2025 Aug 6.
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.
包括转录因子（TFs）的转录调控在内的几种生物学过程是剂量依赖性的。在数学层面，剂量依赖性过程可以通过拟合剂量反应曲线来建模，例如采用希尔型方程。然而，在实验层面，定量调节或调整内源性基因表达以表征剂量依赖性过程具有挑战性。在此，对现有的微调内源性基因表达的方法进行了比较和对比。相对较小的TF剂量变化已被证明是细胞命运决定的基础。尽管如此，由于在内源性和生理条件下缺乏全基因组研究，目前对TFs定量调节基因表达的分子机制的理解仍然有限。最近将TFs的定量扰动与全基因组反应分析相结合的研究正在解开一层未被充分探索的转录控制。与此同时，该领域也出现了新的问题，需要进一步的技术进步才能解决。
