A Model of Nuclear Organization Demonstrates the Effect of Nuclear Envelope - Chromosome Contacts on 3D Organization of Chromosomes

Abstract

We describe a method for modeling organization of the interphase nucleus, and its application to polytene chromosomes of Drosophila salivary glands. The model represents chromosomes as polymer chains confined within the nucleus. Physical parameters of the model are taken directly from experiment, no fitting parameters are introduced. The model is used to simulate chromosome tracing experiments. When applied to previously published data 33 new chromosome_nuclear envelope (Chr-NE) contacts are revealed. Most of these new Chr-NE contacts correspond to intercalary heterochromatin - gene poor, dark staining, late replicating regions of the genome; only three correspond to euchromatin - gene rich, light staining, early replicating regions of the genome. Analysis of regions least likely to form Chr-NE contacts reveals that these are mostly euchromatic, but may contain late replication regions or intercalary heterochromatin. We show that Chr-NE contacts may affect long range gene-gene interactions: depending on the chromosome contour length between two contacts, gene-gene interaction probability may increase or decrease. We also develop methods to objectively quantify chromosome territories and intertwining and discuss the corresponding experimental observations.View Large Image | View Hi-Res Image | Download PowerPoint Slide