Chromatin Structure Shapes the Search Process of Transcription Factors

Event details
Date | 19.08.2016 |
Hour | 12:15 |
Speaker | Nacho Molina, Ph.D., IGBMC Strasbourg, Illkirch (F) |
Location | |
Category | Conferences - Seminars |
BIOENGINEERING SEMINAR
Abstract:
The diffusion of regulatory proteins within the nucleus plays a crucial role in the dynamics of transcriptional regulation. The standard kinetic model assumes a 3D plus 1D diffusion process: regulatory proteins either move freely in solution or slide on linear DNA. However recent single molecule experiments have suggested that 3D structure of chromatin may influence the diffusion process.
In this talk, I will present a novel stochastic diffusion model that integrates high-resolution information on the 3D structure of chromatin with DNA-protein interactions. Thus, the dynamics of transcription factors (TFs) is modelled as a slide plus jump diffusion process on a chromatin network constructed from high-resolution Hi-C data.
Our model allows to uncover the effects of chromatin structure on the diffusion process and provides genome-wide testable predictions for the occupancy profiles of TFs and target search times. Furthermore, we showed that binding sites clustered on a small number of topological associated domains leading to a higher local concentration of TFs. This could reflect an optimal strategy to efficiently use limited transcriptional resources.
Abstract:
The diffusion of regulatory proteins within the nucleus plays a crucial role in the dynamics of transcriptional regulation. The standard kinetic model assumes a 3D plus 1D diffusion process: regulatory proteins either move freely in solution or slide on linear DNA. However recent single molecule experiments have suggested that 3D structure of chromatin may influence the diffusion process.
In this talk, I will present a novel stochastic diffusion model that integrates high-resolution information on the 3D structure of chromatin with DNA-protein interactions. Thus, the dynamics of transcription factors (TFs) is modelled as a slide plus jump diffusion process on a chromatin network constructed from high-resolution Hi-C data.
Our model allows to uncover the effects of chromatin structure on the diffusion process and provides genome-wide testable predictions for the occupancy profiles of TFs and target search times. Furthermore, we showed that binding sites clustered on a small number of topological associated domains leading to a higher local concentration of TFs. This could reflect an optimal strategy to efficiently use limited transcriptional resources.
Practical information
- Informed public
- Free