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Long non-coding RNAs direct the SWI/SNF complex to cell type-specific enhancers

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 central role in cell type- and context-dependent gene expression. Des...

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Main Authors: Oo, James A. (Author) , Warwick, Timothy (Author) , Pálfi, Katalin (Author) , Lam, Frederike (Author) , McNicoll, François (Author) , Prieto García, Cristian (Author) , Günther, Stefan (Author) , Cao, Can (Author) , Zhou, Yinuo (Author) , Gavrilov, Alexey A. (Author) , Razin, Sergey V. (Author) , Cabrera-Orefice, Alfredo (Author) , Wittig, Ilka (Author) , Pullamsetti, Soni Savai (Author) , Kurian, Leo (Author) , Gilsbach, Ralf (Author) , Schulz, Marcel Holger (Author) , Đikić, Ivan (Author) , Müller-McNicoll, Michaela (Author) , Brandes, Ralf (Author) , Leisegang, Matthias (Author)
Format: Article (Journal)
Language:English
Published: 02 January 2025
In: Nature Communications
Year: 2025, Volume: 16, Pages: 1-13
ISSN:2041-1723
DOI:10.1038/s41467-024-55539-6
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-024-55539-6
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-024-55539-6
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Author Notes:James A. Oo, Timothy Warwick, Katalin Pálfi, Frederike Lam, Francois McNicoll, Cristian Prieto-Garcia, Stefan Günther, Can Cao, Yinuo Zhou, Alexey A. Gavrilov, Sergey V. Razin, Alfredo Cabrera-Orefice, Ilka Wittig, Soni Savai Pullamsetti, Leo Kurian, Ralf Gilsbach, Marcel H. Schulz, Ivan Dikic, Michaela Müller-McNicoll, Ralf P. Brandes, Matthias S. Leisegang
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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 central role in cell type- and context-dependent gene expression. Despite the absence of a defined DNA recognition motif, SWI/SNF binds lineage specific enhancers genome-wide where it actively maintains open chromatin state. It does so while retaining the ability to respond dynamically to cellular signals. However, the mechanisms that guide SWI/SNF to specific genomic targets have remained elusive. Here we demonstrate that trans-acting long non-coding RNAs (lncRNAs) direct the SWI/SNF complex to cell type-specific enhancers. SWI/SNF preferentially binds lncRNAs and these predominantly bind DNA targets in trans. Together they localize to enhancers, many of which are cell type-specific. Knockdown of SWI/SNF- and enhancer-bound lncRNAs causes the genome-wide redistribution of SWI/SNF away from enhancers and a concomitant differential expression of spatially connected target genes. These lncRNA-SWI/SNF-enhancer networks support an enhancer hub model of SWI/SNF genomic targeting. Our findings reveal that lncRNAs competitively recruit SWI/SNF, providing a specific and dynamic layer of control over chromatin accessibility, and reinforcing their role in mediating enhancer activity and gene expression.
Item Description:Gesehen am 16.01.2026
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-024-55539-6

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