Division of Molecular Genetics and Centre for Biomedical Genetics, Netherlands Cancer Institute, Amsterdam, The Netherlands.
PLoS Genet. 2011 Mar;7(3):e1001343. doi: 10.1371/journal.pgen.1001343. Epub 2011 Mar 24.
Polycomb group (PcG) proteins bind and regulate hundreds of genes. Previous evidence has suggested that long-range chromatin interactions may contribute to the regulation of PcG target genes. Here, we adapted the Chromosome Conformation Capture on Chip (4C) assay to systematically map chromosomal interactions in Drosophila melanogaster larval brain tissue. Our results demonstrate that PcG target genes interact extensively with each other in nuclear space. These interactions are highly specific for PcG target genes, because non-target genes with either low or high expression show distinct interactions. Notably, interactions are mostly limited to genes on the same chromosome arm, and we demonstrate that a topological rather than a sequence-based mechanism is responsible for this constraint. Our results demonstrate that many interactions among PcG target genes exist and that these interactions are guided by overall chromosome architecture.
多梳抑制复合物(PcG)蛋白结合并调节数百个基因。先前的证据表明,长程染色质相互作用可能有助于 PcG 靶基因的调控。在这里,我们采用了染色质构象捕获芯片(4C)技术,系统地绘制了果蝇幼虫脑组织中的染色体相互作用图谱。我们的结果表明,PcG 靶基因在核空间中相互作用广泛。这些相互作用对 PcG 靶基因具有高度特异性,因为低表达或高表达的非靶基因显示出不同的相互作用。值得注意的是,相互作用主要局限于同一染色体臂上的基因,我们证明拓扑结构而不是基于序列的机制负责这种约束。我们的结果表明,PcG 靶基因之间存在许多相互作用,并且这些相互作用受到整体染色体结构的指导。