Colloquium- “Revealing nuclear secrets: how polymer dynamics and protein diffusion control gene expression” with Prof. Arpita Upadhyaya (University of Maryland)
Colloquium
February 12, 2025
3:00 PM - 4:00 PM
Location
238 2SES
Calendar
Download iCal File"Revealing nuclear secrets: how polymer dynamics and protein diffusion control gene expression"
Prof. Arpita Upadhyaya
Department of Physics
University of Maryland
Abstract: The cell nucleus contains the genetic material necessary for the synthesis of cellular components and propagation of information. The meters long DNA is packed into a micron-sized nucleus in a highly organized manner. Genomic techniques have established the basic structural rules of hierarchical organization of chromatin but they offer only a static, cell-averaged snapshot. Chromatin is a highly dynamic polymer that is embedded in a viscoelastic solvent and subject to active, far-from equilibrium forces. As a result, chromatin exhibits dynamics at multiple time scales, ranging from the sub-second scale thermal motion of the chromatin polymer to minutes and hours long reorganization in response to developmental programs and external chemical and mechanical stimuli. How information is read out in this dynamic environment to regulate gene expression remains poorly understood. Transcription factors (TFs) are specialized proteins which regulate gene expression by binding to specific DNA sequences within a complex and heterogeneous chromatin environment to assemble transcriptional machinery. Single-molecule tracking (SMT) has emerged as a powerful approach to explore chromatin and TF dynamics within nuclei of living cells. We found that TFs follow power-law distributed binding times, suggesting that the prevalent model of specific and non-specific TF/chromatin interactions is incomplete. Using machine-learning based analysis of single molecule mobility, we show that chromatin displays two distinct low-mobility states. Our experimental observations are consistent with a minimal active copolymer model for interphase chromosomes. Remarkably, we find that a diverse set of transcription factors, co-regulators and remodelers also exhibit two distinct low-mobility states. Mutational analysis reveals the physical and molecular origins of the two states and their functional roles. Together, our results elucidate how the dynamics of transcription factors and chromatin regulate gene expression in mammalian cells.
Date posted
Jan 7, 2025
Date updated
Feb 10, 2025