Active and repressed biosynthetic gene clusters have spatially distinct chromosome states

03 de junio de 2020

 

Te invitamos a leer el artículo "Active and repressed biosynthetic gene clusters have spatially distinct chromosome states", publicado recientemente en la revista PNAS, una investigación de la Dra. Selene Fernández, Profesor Investigador del Laboratorio de Genómica Funcional y Evolutiva de ARNS Regulatorios colaborando con los alumnos Jesús Emiliano Sotelo-Fonseca y América Ramírez Colmenero de la UGA-Langebio e investigadores Hans-Wilhelm Nützmann, Daniel Doerr, Eva Wegel, Marco Di Stefano, Steven W. Wingett, Peter Fraser, Laurence Hurst, Anne Osbourn.

Autores: Hans-Wilhelm Nützmann, Daniel Doerr, América Ramírez-Colmenero, Jesús Emiliano Sotelo-Fonseca, Eva Wegel, Marco Di Stefano, Steven W. Wingett, Peter Fraser, Laurence Hurst, Selene L. Fernandez-Valverde, and Anne Osbourn.

Felicitamos al estudiantado y profesorado que contribuyeron en esta investigación por su arduo trabajo.

Abstract: 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 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.

Keywords: gene cluster, Hi-C, Arabidopsis thaliana, H3K27ME3, chromosome organization.

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