How Transcription\nFactors Binding Stimulates Transcriptional\nBursting

Transcription is a fundamental biological process of\ntransferring\ngenetic information which often occurs in stochastic bursts when periods\nof intense activity alternate with quiescent phases. Recent experiments\nidentified strong correlations between the association of transcription\nfactors (TFs) to gene promoters on DNA and transcriptional activity.\nHowever, the underlying molecular mechanisms of this phenomenon remain\nnot well understood. Here, we present a theoretical framework that\nallowed us to investigate how binding dynamics of TF influences transcriptional\nbursting. Our minimal theoretical model incorporates the most relevant\nphysical-chemical features, including TF exchange among multiple binding\nsites at gene promoters and TF association/dissociation dynamics.\nUsing analytical calculations supported by Monte Carlo computer simulations,\nit is demonstrated that transcriptional bursting dynamics depends\non the strength of TF binding and the number of binding sites. Stronger\nTF binding affinity prolongs burst duration but reduces variability,\nwhile an optimal number of binding sites maximizes transcriptional\nnoise, facilitating cellular adaptation. Our theoretical method explains\navailable experimental observations quantitatively, confirming the\nmodel’s predictive accuracy. This study provides important\ninsights into molecular mechanisms of gene expression and regulation,\noffering a new theoretical tool for understanding complex biological\nprocesses.