Sub-diffusion and Compartmentalization: How the Nuclear Pore Complex and Stochastic Movement are Utilized to Dynamically Organize the Eukaryotic Genome


In nearly all Eukaryotes, the membrane-enclosed nucleus contains the vast majority of the cellular genome. Within this sub-cellular compartment, the nuclear architecture facilitates genomic chromatin organization. Controlling chromosomal loci’s spatial positioning relative to subnuclear structures and each other can have local and global effects on gene expression. Moreover, chromatin organization can vary widely between species and even tissues within a multicellular organism. Determining how genes organize to establish and maintain transcriptional states is necessary for understanding this ancient, conserved method for epigenetic expression regulation. Within Saccharomyces cerevisiae, commonly known as brewer’s yeast, hundreds of genes are known to interact with the Nuclear Pore Complex, become organized at the periphery, and form clusters of similarly regulated genes. Tracking these organized genes reveals that chromatin association with the Nuclear Pore Complex is dynamic and positioning at the nuclear periphery is the product of repetitive binding and disassociation events. Furthermore, interchromosomal gene clusters appear to coordinate movement vectors between loci through a mechanism that is still being elucidated. Dynamic repositioning between sub-nuclear compartments also occurs through a largely stochastic mechanism that relies on sub-diffusive gene locus movement, random collision with the Nuclear Pore Complex or other nuclear architecture, and momentary but repeated binding between the two elements. Developing a modular and widely applicable model for gene movement within Eukaryotes has allowed for simulating locus trajectories, generating better hypotheses for organizational mechanisms, and predict stochastic movement given conditions only achievable in silico. Taken together, this work explains how stochastic movement is sufficient for establishing dynamic gene positioning in the yeast nucleus and lays the foundation for further understanding more complex genome organization phenomena that impact the transcriptome and proteome.

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