Control of gene expression by modulated self-assembly

Numerous transcription factors self-assemble into different order oligomeric species in a way that is actively regulated by the cell. Until now, no general functional role has been identified for this widespread process. Here, we capture the effects of modulated self-assembly in gene expression with a novel quantitative framework. We show that this mechanism provides precision and flexibility, two seemingly antagonistic properties, to the sensing of diverse cellular signals by systems that share common elements present in transcription factors like p53, NF-kappa B, STATs, Oct and RXR. Applied to the nuclear hormone receptor RXR, this framework accurately reproduces a broad range of classical, previously unexplained, sets of gene expression data and corroborates the existence of a precise functional regime with flexible properties that can be controlled both at a genome-wide scale and at the individual promoter level.

Surface-Bound Selectin-Ligand Binding Is Regulated By Carrier Diffusion

Two-dimensional (2D) kinetics of receptor-ligand interactions governs cell adhesion in many biological processes. While the dissociation kinetics of receptor-ligand bond is extensively investigated, the association kinetics has much less been quantified. Recently receptor-ligand interactions between two surfaces were investigated using a thermal fluctuation assay upon biomembrane force probe technique (Chen et al. in Biophys J 94:694-701, 2008). The regulating factors on association kinetics, however, are not well characterized. Here we developed an alternative thermal fluctuation assay using optical trap technique, which enables to visualize consecutive binding-unbinding transition and to quantify the impact of microbead diffusion on receptor-ligand binding. Three selectin constructs (sLs, sPs, and PLE) and their ligand P-selectin glycoprotein ligand 1 were used to conduct the measurements. It was indicated that bond formation was reduced by enhancing the diffusivity of selectin-coupled carrier, suggesting that carrier diffusion is crucial to determine receptor-ligand binding. It was also found that 2D forward rate predicted upon first-order kinetics was in the order of sPs > sLs > PLE and bond formation was history-dependent. These results further the understandings in regulating association kinetics of surface-bound receptor-ligand interactions.