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

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 prooncogenic 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.

LncRNA NRON Inhibits Osteosarcoma Cell Proliferation, Invasion by Regulating MVB12B

“…Lnc-CCDST promotes DHX9 degradation by serving as a scaffold to facilitate the formation of MDM2 and DHX9 complexes [23]. In epigenetic regulation, SWINGN in uences the ability of the SWI/SNF complexes to drive epigenetic activation of speci c promoters, suggesting a SWI/SNF-RNA cooperation to achieve optimal transcriptional activation [24]. Previous studies have shown that LncRNA NRON alleviates atrial brosis via promoting NFATc3 phosphorylation [16].…”

SMARCB1 Acts as a Quiescent Gatekeeper for Cell Cycle and Immune Response in Human Cells

“…We observed that SMARCB1 knockdown-induced upregulation of IL6 was further enhanced in the presence of human IL1β (hIL1β) (Figure 4b), suggesting that SMARCB1 was in the mainstream of IL6 regulation. To investigate how SMARCB1 regulated the level of IL6 expression, we examined whether SMARCB1 bound to the DNA regulatory region of known IL6 upstream regulators and whether the gene expression was altered according to the presence or absence of SMARCB1 [40][41][42]. While the transcription level of these genes did not significantly change in our system ( Figure S1b), we found that SMARCB1 bound to the regulatory region of activator nuclear factor-κB subunit (NF-κB) 1, repressor tumor protein p53 (TP53), stabilizer AT-rich interactive domain-containing protein 5A (ARIDA5), and degrader ZC2H12A in human BJ fibroblasts ( Figure S1c).…”

Identification of Hub Genes Associated with Melanoma Development by Comprehensive Bioinformatics Analysis

“…Weighted gene co-expression network analysis (WGCNA), one of the bioinformatics analysis methods, describes co-expression patterns between genes in microarray samples, providing new insights for predicting the function of co-expressed genes and the development of diseases [7]. Differentially expressed genes(DEGs) are widely used in cancer research and are excellent cancer research methods [8][9][10]. It provides a genomics-based method for discovering changes in gene expression levels between experimental and control groups [11].…”