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| Status |
Public on Nov 27, 2024 |
| Title |
LncRNA adapters determine SWI/SNF complex occupancy at gene regulatory elements [CUT&Run] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The coordination of chromatin remodeling is essential for DNA accessibility and gene expression control. The highly conserved and ubiquitously expressed SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex plays a key role in regulating gene expression in a context-dependent manner. SWI/SNF actively maintains open chromatin states across the genome and responds dynamically to cellular signals. However, the precise mechanisms determining how SWI/SNF is targeted to specific genomic sites remain elusive. In this study we demonstrate that long non-coding RNAs (lncRNAs) are pivotal in the binding of the SWI/SNF complex to specific genomic targets. The interaction between SWI/SNF and lncRNAs is essential for the recruitment of the complex to gene regulatory elements, where it plays a critical role. We show that trans-acting lncRNAs direct the SWI/SNF complex to cell-specific enhancers, with lncRNA knockdowns leading to a genome-wide redistribution of SWI/SNF away from these enhancers. This redistribution impacts the expression of genes connected to these enhancers, underscoring the critical role of lncRNAs in the specific targeting of SWI/SNF to DNA. This insight into the targeting mechanisms of SWI/SNF by lncRNAs has broad implications, from understanding the processes of gene expression control to identifying therapeutic targets in diseases associated with SWI/SNF dysfunction, such as cancer.
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| Overall design |
To investigate which gene regulatory elements depend on lncRNA-recruited BRG1 for their chromatin accessibility, BRG1 CUT&RUN was performed in HUVEC after lncRNA knockdown, which in some cases was followed by overexpression of the given lncRNA to rescue the effects.
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| Contributor(s) |
Oo JA, Warwick T, Leisegang MS, Brandes RP |
| Citation missing |
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| |
| Submission date |
Sep 29, 2024 |
| Last update date |
Nov 27, 2024 |
| Contact name |
Timothy Warwick |
| E-mail(s) |
[email protected]
|
| Organization name |
Goethe Universität Frankfurt am Main
|
| Department |
Institute for Cardiovascular Physiology
|
| Street address |
Theodor-Stern-Kai 7
|
| City |
Frankfurt am Main |
| State/province |
Hesse |
| ZIP/Postal code |
60590 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (5)
|
| GSM8545762 |
HUVEC, BRG1 CUT&RUN, siMIR100HG |
| GSM8545763 |
HUVEC, BRG1 CUT&RUN, siMIR100HG + overexpression MIR100HG |
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| This SubSeries is part of SuperSeries: |
| GSE262070 |
LncRNA adapters determine SWI/SNF complex occupancy at gene regulatory elements |
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| Relations |
| BioProject |
PRJNA1166936 |
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