A lncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions.,Nature Communications

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A lncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions.
Nature Communications ( IF 14.7 ) Pub Date : 2020-02-18 , DOI: 10.1038/s41467-020-14623-3
Elena Grossi _{1,

2} , Ivan Raimondi _{1,

2} , Enrique Goñi _{1,

2} , Jovanna González _{1,

2} , Francesco P Marchese _{1,

2} , Vicente Chapaprieta ₃ , José I Martín-Subero _{3,

4,

5,

6} , Shuling Guo ₇ , Maite Huarte _{1,

2}

Affiliation

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.

中文翻译：

lncRNA-SWI/SNF 复合体串扰控制特定启动子区域的转录激活。

LncRNA 已被证明是染色质调控的直接参与者，但对其在活跃基因组位点中的作用知之甚少。我们通过分析增殖和衰老条件下含有 SMARCB1 的 SWI/SNF 复合物的 RNA 相互作用组来研究 lncRNA 在基因激活中的作用。SMARCB1 相关转录本的分离以及染色质分析表明，SMARCB1 与局部转录 RNA 差异结合的活性区域存在普遍关联。我们鉴定出 SWINGN，一种仅在增殖条件下与 SMARCB1 相互作用的 lncRNA，在某些肿瘤类型中发挥促癌作用。SWINGN 由增强子转录，并通过有利于 SMARCB1 结合来调节 GAS6 癌基因的激活，作为拓扑组织区域的一部分，以及更大的促癌基因网络。我们的结果表明，SWINGN 影响 SWI/SNF 复合物驱动特定启动子表观遗传激活的能力，表明 SWI/SNF-RNA 合作以实现最佳转录激活。

更新日期：2020-02-18

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