Active and repressed biosynthetic gene clusters have spatially distinct chromosome states

Abstract

<jats:p>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 in<jats:italic>Arabidopsis thaliana</jats:italic>. 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.</jats:p>

Evolutionary conserved protein motifs drive attachment of the plant nucleoskeleton at nuclear pores

“…Indeed, rapid responses involving one or several of the NUPs, KAKU4 and CRWN proteins have been reported during hyperosmotic stress (71), in response to copper in the medium (76) or upon biotic stress (77). Consistently, several examples suggest that gene expression in plants is influenced by the positioning of genes in respect to the nuclear periphery (76, 78–80). As such, the nucleoskeleton may play a central role by recruiting specific chromatin domains at the nuclear periphery (21, 74).…”

Chromosome-level genome assembly of Ophiorrhiza pumila reveals the evolution of camptothecin biosynthesis

“…The scattered nature of metabolic gene clusters seems to be prevalent across plant genomes, as observed in the case of MIA gene clusters, as well as previously reported secondary metabolic gene clusters in other plant species 55 , 58 . With the complexities associated with the regulation of gene-expression in plants, it is only rational to suggest that physical proximity may not be sufficient to facilitate coexpression among genes within a gene cluster 57 . On the other hand, gene clusters represent discrete genome segments that serve as the hotspots for retaining and evolving specialized metabolite biosynthesis.…”

Subnuclear gene positioning through lamina association affects copper tolerance

“…In addition, recently, CRWN1binding regions that are similar to NUP1-binding regions were also reported 26 . Silenced biosynthetic gene clusters approach the nuclear periphery, while activated clusters relocate away from it 37 . Other studies found that chromocenters are specifically localized at the nuclear periphery 38 .…”