While colocalization within a bacterial operon enables coexpression of the constituent genes, the mechanistic logic of clustering of nonhomologous monocistronic genes in eukaryotes is not immediately obvious. Biosynthetic gene clusters that encode pathways for specialized metabolites are an exception to the classical eukaryote rule of random gene location and provide paradigmatic exemplars with which to understand eukaryotic cluster dynamics and regulation. Here, using 3C, Hi-C, and Capture Hi-C (CHi-C) organ-specific chromosome conformation capture techniques along with high-resolution microscopy, we investigate how chromosome topology relates to transcriptional activity of clustered biosynthetic pathway genes inArabidopsis thaliana. Our analyses reveal that biosynthetic gene clusters are embedded in local hot spots of 3D contacts that segregate cluster regions from the surrounding chromosome environment. The spatial conformation of these cluster-associated domains differs between transcriptionally active and silenced clusters. We further show that silenced clusters associate with heterochromatic chromosomal domains toward the periphery of the nucleus, while transcriptionally active clusters relocate away from the nuclear periphery. Examination of chromosome structure at unrelated clusters in maize, rice, and tomato indicates that integration of clustered pathway genes into distinct topological domains is a common feature in plant genomes. Our results shed light on the potential mechanisms that constrain coexpression within clusters of nonhomologous eukaryotic genes and suggest that gene clustering in the one-dimensional chromosome is accompanied by compartmentalization of the 3D chromosome.

Long non-coding RNAs (lncRNAs) have important regulatory functions across eukarya. It is now clear that many of these functions are related to gene expression regulation through their capacity to recruit epigenetic modifiers and establish chromatin interactions. Several lncRNAs have been recently shown to participate in modulating chromatin within the spatial organization of the genome in the three-dimensional space of the nucleus. The identification of lncRNA candidates is challenging, as it is their functional characterization. Conservation signatures of lncRNAs are different from those of protein-coding genes, making identifying lncRNAs under selection a difficult task, and the homology between lncRNAs may not be readily apparent. Here, we review the evidence for these higher-order genome organization functions of lncRNAs in animals and the evolutionary signatures they display.

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