Guided nuclear exploration increases CTCF target search efficiency

摘要: Mammalian genomes are enormous. For a DNA-binding protein, this means that the number of non-specific, off-target sites vastly exceeds specific, cognate sites. How mammalian proteins overcome challenge to efficiently locate their target is not known. Here through live-cell single-molecule tracking, we show CCCTC-binding factor, CTCF, repeatedly trapped in small zones nucleus manner largely dependent on its RNA-binding region (RBR). Integrating theory, devise new model, Anisotropic Diffusion transient Trapping Zones (ADTZ), explain this. Functionally, RBR-mediated trapping increases efficiency CTCF search by 2.5 fold. Since RBR-domain also mediates clustering, our results suggest guided mechanism where clusters concentrate diffusing near binding sites, thus increasing local ON-rate. We guiding may represent general cells.