Chromosome structure at metabolic gene clusters

Functionally related genes that determine multi-step processes in plants, such as genes for primary metabolic pathways or developmental processes, are typically dispersed throughout the genome. Biosynthetic gene clusters that encode pathways for specialised metabolites are an exception to this rule and resemble gene order in bacteria. We have recently shown that such biosynthetic gene cluster in diverse species have characteristic epigenetic signatures. Here, we investigate how chromosome topology relates to transcriptional activity of clustered metabolic pathway genes using different organ specific chromosome conformation capture techniques and high-resolution microscopy. Our analyses reveal that silenced clusters associate with heterochromatic chromosomal domains towards the periphery of the nucleus, while transcriptionally active clusters re-locate away from the nuclear periphery. We further show that the biosynthetic gene clusters are embedded in local hot-spots of three-dimensional contacts. These local topological conformations differ between active and silenced clusters. Our analyses provide a high-resolution view of the large-scale 3D chromosomal reconfigurations that accompany transcriptional changes at co-ordinately regulated gene groups in a compact eukaryotic genome. We speculate that selective global and local chromosomal re-organisation is crucial for effective transcriptional control of co-localised and functionally related genes.