Active and repressed biosynthetic gene clusters have spatially distinct chromosome states

Hans-Wilhelm Nützmann, Daniel Doerr, America Ramirez-Colmenero, Jesus Emiliano Sotelo-Fonseca, Eva Wegel, Marco Di Stefano, Steven W. Wingett, Peter Fraser, Laurence Hurst, Selene L. Fernandez-Valverde, Anne Osbourn

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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 highresolution microscopy, we investigate how chromosome topology relates to transcriptional activity of clustered biosynthetic pathway genes in Arabidopsis 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.

Original languageEnglish
Pages (from-to)13800-13809
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
Early online date3 Jun 2020
Publication statusPublished - 16 Jun 2020


  • Arabidopsis thaliana
  • Chromosome organization
  • Gene cluster
  • H3K27me3
  • Hi-C

ASJC Scopus subject areas

  • General


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