A lncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions

Elena Grossi, Ivan Raimondi, Enrique Goñi, Jovanna González, Francesco P. Marchese, Vicente Chapaprieta, José I. Martín-Subero, Shuling Guo and Maite Huarte ()
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Elena Grossi: University of Navarra
Ivan Raimondi: University of Navarra
Enrique Goñi: University of Navarra
Jovanna González: University of Navarra
Francesco P. Marchese: University of Navarra
Vicente Chapaprieta: Universitat de Barcelona
José I. Martín-Subero: Universitat de Barcelona
Shuling Guo: Ionis Pharmaceuticals
Maite Huarte: University of Navarra

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract LncRNAs have been shown to be direct players in chromatin regulation, but little is known about their role at active genomic loci. We investigate the role of lncRNAs in gene activation by profiling the RNA interactome of SMARCB1-containing SWI/SNF complexes in proliferating and senescent conditions. The isolation of SMARCB1-associated transcripts, together with chromatin profiling, shows prevalent association to active regions where SMARCB1 differentially binds locally transcribed RNAs. We identify SWINGN, a lncRNA interacting with SMARCB1 exclusively in proliferating conditions, exerting a pro-oncogenic role in some tumor types. SWINGN is transcribed from an enhancer and modulates the activation of GAS6 oncogene as part of a topologically organized region, as well as a larger network of pro-oncogenic genes by favoring SMARCB1 binding. Our results indicate that SWINGN influences the ability of the SWI/SNF complexes to drive epigenetic activation of specific promoters, suggesting a SWI/SNF-RNA cooperation to achieve optimal transcriptional activation.

Date: 2020
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DOI: 10.1038/s41467-020-14623-3

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