Interactions among Polycomb Domains Are Guided by Chromosome Architecture

Interactions among Polycomb Domains Are Guided by Chromosome Architecture: "Author Summary

The folding of chromosomes inside the cell nucleus is a fascinating yet poorly understood topological problem. It is thought that certain genomic loci that are distant in the linear genome may come together in nuclear space by folding of the chromosome fiber. Previously, such a long-range interaction was found in Drosophila for two genomic loci that are known to be bound by the Polycomb Repressive Complex. Because hundreds of genes are known to be bound by Polycomb proteins, we asked whether such long-range contacts are more common. To address this, we optimized the Chromosome Conformation Capture on Chip (4C) technology for use in small tissue samples. Using this technique in dissected larval brains, we found that indeed Polycomb target genes interact frequently with each other, even when they are separated by megabases of sequence. However, these long-range interactions occur almost exclusively on the same chromosome arm. By using a rearranged chromosome in which segments are swapped between two arms, we demonstrate that not DNA sequence but chromosome architecture imposes this restriction. Taken together, our data demonstrate that Polycomb target genes extensively interact in nuclear space, but only when they are located on the same chromosome arm.

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