title: ÐÐµÑÐ°Ð²Ð½Ð¾Ð²ÐµÑÐ½ÑÐµ Ð¼Ð¾Ð´ÐµÐ»Ð¸ ÑÐµÐ³ÑÐ»ÑÑÐ¸Ð¸ Ð³ÐµÐ½Ð¾Ð²
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¼Ð°Ð³Ð¸ÑÑÑÐ°
titleType: Subtitle
title: Non-equilibrium models of gene regulation
Creators: name: ÐÐµÐ»ÑÐ½Ð¸ÐºÐ¾Ð²Ð°, ÐÐ½Ð½Ð°
Publisher: name: Ð¡Ð°Ð½ÐºÑ-ÐÐµÑÐµÑÐ±ÑÑÐ³ÑÐºÐ¸Ð¹ Ð¿Ð¾Ð»Ð¸ÑÐµÑÐ½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÐ½Ð¸Ð²ÐµÑÑÐ¸ÑÐµÑ ÐÐµÑÑÐ° ÐÐµÐ»Ð¸ÐºÐ¾Ð³Ð¾
Year: 2023
Subjects: ÐÐ°ÑÐµÐ¼Ð°ÑÐ¸ÐºÐ° Ð¿ÑÐ¸ÐºÐ»Ð°Ð´Ð½Ð°Ñ
ÐÐ½ÑÐ¾ÑÐ¼Ð°ÑÐ¸ÐºÐ°
ÑÐµÐ³ÑÐ»ÑÑÐ¸Ñ ÑÑÐºÐ°ÑÐ¸Ð¾ÑÐ¸ÑÐµÑÐºÐ¾Ð¹ ÑÑÐ°Ð½ÑÐºÑÐ¸Ð¿ÑÐ¸Ð¸
ÑÑÐ°Ð½ÑÐºÑÐ¸Ð¿ÑÐ¸Ð¾Ð½Ð½ÑÐµ ÑÐ°ÐºÑÐ¾ÑÑ
Ð½ÐµÑÐ°Ð²Ð½Ð¾Ð²ÐµÑÐ½Ð¾Ðµ Ð¼Ð¾Ð´ÐµÐ»Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ðµ
ÑÐµÐ³ÑÐ»ÑÑÐ¾ÑÐ½ÑÐµ ÑÐµÐ½Ð¾ÑÐ¸Ð¿Ñ
transcriptional regulation in eukaryotes
transcription factors
non-equilibrium modeling
regulatory phenotypes

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description: The work is devoted to the development of a modified non-equilibrium thermodynamic model of gene regulation that takes into account the real features of the regulatory process in eukaryotes. The proposed transcription initiation model includes an ensemble of transcription factor (TF) binding sites to DNA with an affinity gradient instead of an ensemble of identical sites considered in the basic model. Within the framework of the new model, three âregulatory phenotypesâ characterizing the efficiency of gene regulation were identified, and their numerical analysis was carried out using equilibrium and non-equilibrium approaches. Regulatory phenotypes included residence time of a TF on DNA, specificity of transmission of the regulatory signal to the target gene, and sensitivity to the regulatory signal. Scenarios are described when a non-equilibrium model of regulation demonstrates advantages over an equilibrium model in terms of regulatory phenotypes. It is shown how taking into account the affinity gradient of TF-DNA binding sites affects regulatory phenotypes. It was shown that the modified model makes it possible to achieve greater sensitivity to the regulatory signal with a shorter residence time of TF on DNA than in the basic model. At a given level of gene expression, the modified model demonstrates an increase in maximum specificity with an increase in the number of TF-DNA binding sites, and this effect is possible only in a non-equilibrium approach. The modification of the model proposed in this work shows promise of a non-equilibrium approach to modeling regulatory processes for eukaryotic cells characterized by a wide variety of TF-DNA binding sites. The model allows you to reflect the features of the regulatory process without increasing the number of model parameters by several times. It is shown how the considered approach can be generalized to the case of the short-range transcriptional repression model. The results obtained provide new information about the features of gene regulation associated with the possible non-equilibrium nature of this process.