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Title:
A lncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions | Nature Communications
Description:
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. SWI/SNF complexes regulate chromatin architecture and gene expression. Here the authors report the RNA interactome of SMARCB1-containing SWI/SNF complexes, showing the function of SMARCB1-interacting long noncoding RNA SWINGN in transcriptional activation of GAS6 and a set of SWI/SNF target genes.
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headline:A lncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions
description: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. SWI/SNF complexes regulate chromatin architecture and gene expression. Here the authors report the RNA interactome of SMARCB1-containing SWI/SNF complexes, showing the function of SMARCB1-interacting long noncoding RNA SWINGN in transcriptional activation of GAS6 and a set of SWI/SNF target genes.
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Chromatin
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headline:A lncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions
description: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. SWI/SNF complexes regulate chromatin architecture and gene expression. Here the authors report the RNA interactome of SMARCB1-containing SWI/SNF complexes, showing the function of SMARCB1-interacting long noncoding RNA SWINGN in transcriptional activation of GAS6 and a set of SWI/SNF target genes.
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name:Maite Huarte
url:http://orcid.org/0000-0003-3753-6493
affiliation:
name:University of Navarra
address:
name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
type:PostalAddress
type:Organization
name:Institute of Health Research of Navarra (IdiSNA)
address:
name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
name:Departament de Fonaments Clinics, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain
name:Departament de Fonaments Clinics, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain
name:Institut dâInvestigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
name:Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
name:Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
name:Department of Antisense Drug Discovery and Clinical Development, Ionis Pharmaceuticals, Carlsbad, USA
name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
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