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The effect of chromosome-nuclear envelope attachments on 3D genome organization Nick Kinney, Alexey Onufriev, Igor Sharakhov
Genetics Bioinformatics and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, nak3c@vt.edu Department of Computer Science, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, alexey@cs.vt.edu Entomology Department, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, igor@vt.edu

We build computational models of the polytene chromosomes from Drosophila salivary gland nuclei. The chromosomes, bounded by the nuclear envelope, are modeled as random selfavoiding walks under confinement. We use three ensembles of computational nuclei to determine the effects of chromosome-nuclear envelope (Chr-NE) attachments on the 3D organization of the genome: each ensembles includes approximately 3000 nuclei with 0, 15, and 48 Chr-NE attachments respectively. Both the number and distribution of Chr-NE attachments in these three ensembles bring about changes in the 3D organization of chromosomes. Increasing the number of Chr-NE attachments drastically decreases the probability of inter-arm chromosome contacts with a more modest decrease in the probability of intra-arm chromosome contacts. Changing the distribution of Chr-NE attachments repositions the chromosomes with respect to the NE: chromosome regions with the fewest Chr-NE attachments are repositioned toward the center of the nucleus while those with the most Chr-NE are repositioned toward the periphery. A simple lattice model is used to explain why Chr-NE attachments induce these changes in our computational nuclei.