Transcription-mediated supercoiling regulates genome folding and loop formation

The chromatin fiber folds into loops, but the mechanisms controlling loop extrusion are still poorly understood. Using super-resolution microscopy, we visualize that loops in intact nuclei are formed by a scaffold of cohesin complexes from which the DNA protrudes. RNA polymerase II decorates the top...

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Detalles Bibliográficos
Autores: Neguembor, Maria Victoria, Martin, Laura, Castells García, Àlvaro, 1991-, Gómez García, Pablo, Vicario, Chiara, Carnevali, Davide, Abed, Jumana AlHaj, Granados, Alba, Sebastián Pérez, Rubén, Sottile, Francesco, 1988-, Solon, Jérôme, Wu, Chao-Ting, Lakadamyali, Melike, Cosma, Maria Pia, 1970-
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/48422
Acceso en línea:http://hdl.handle.net/10230/48422
http://dx.doi.org/10.1016/j.molcel.2021.06.009
Access Level:acceso abierto
Palabra clave:STORM microscopy
Cohesin
Genome folding
Super-resolution microscopy
Supercoiling
Transcription
Descripción
Sumario:The chromatin fiber folds into loops, but the mechanisms controlling loop extrusion are still poorly understood. Using super-resolution microscopy, we visualize that loops in intact nuclei are formed by a scaffold of cohesin complexes from which the DNA protrudes. RNA polymerase II decorates the top of the loops and is physically segregated from cohesin. Augmented looping upon increased loading of cohesin on chromosomes causes disruption of Lamin at the nuclear rim and chromatin blending, a homogeneous distribution of chromatin within the nucleus. Altering supercoiling via either transcription or topoisomerase inhibition counteracts chromatin blending, increases chromatin condensation, disrupts loop formation, and leads to altered cohesin distribution and mobility on chromatin. Overall, negative supercoiling generated by transcription is an important regulator of loop formation in vivo.