The Pattern of Chromosome Folding in Interphase Is Outlined by the Linear Gene Density Profile

Abstract

Spatial organization of chromatin in the interphase nucleus plays a role in gene expression and inheritance. Although it appears not to be random, the principles of this organization are largely unknown. In this work, we show an explicit relationship between the intranuclear localization of various chromosome segments and the pattern of gene distribution along the genome sequence. Using a 7-megabase-long region of the Drosophila melanogaster chromosome 2 as a model, we observed that the six gene-poor chromosome segments identified in the region interact with components of the nuclear matrix to form a compact stable cluster. The six gene-rich segments form a spatially segregated unstable cluster dependent on nonmatrix nuclear proteins. The resulting composite structure formed by clusters of gene-rich and gene-poor regions is reproducible between the nuclei. We suggest that certain aspects of chromosome folding in interphase are predetermined and can be inferred through in silico analysis of chromosome sequence, using gene density profile as a manifestation of “folding code.”

ACKNOWLEDGMENTS

This work was supported by grant GM61549 from the U.S. Public Health Service.

We are indebted to W. Brunken, J. Fitch, E. Gibney, and M. Nurminskaya for valuable comments and careful reading of the manuscript, and we sincerely thank W. Brunken for kindly providing access to the imaging equipment.