Stochastic Systems Biology of Gene Regulation

Stochastic Systems Biology of Gene Regulation

Gene regulation is a multi-step process that plays a central role in shaping the cell response to environmental stimuli. First, pioneer transcription factors (TFs) recognize sequence-specific DNA-binding sites at gene promoters and regulatory sites. Then, specific enzymes are recruited which post-translationally modify the histone tails and cause nucleosome remodeling. Additional TFs bind in accessible chromatin regions and ultimately RNA polymerase initiates mRNA synthesis. These reactions occur in a crowded nucleus where chromatin forms a complex 3D structure. Moreover, stochastic fluctuations cause that gene expression dynamics in single cells deviates significantly from the average behavior at the population level.


New experimental technologies allow us to measure Protein-DNA interactions, post-transcriptional histone modifications and chromatin 3D structure genome-wide in populations and more recently in single cells. Time-course experiments using these methods present a unique opportunity to study, in a quantitative manner, the dynamics of gene regulation.


The main research activity in our group is to build stochastic biophysical models of eukaryotic gene regulation by integrating all these data sets. We used principle-based methods rooted in bioinformatics, Bayesian statistics, stochastic processes and statistical mechanics.



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