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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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Hauptverfasser: Oo, James A. (VerfasserIn) , Warwick, Timothy (VerfasserIn) , Pálfi, Katalin (VerfasserIn) , Lam, Frederike (VerfasserIn) , McNicoll, François (VerfasserIn) , Prieto García, Cristian (VerfasserIn) , Günther, Stefan (VerfasserIn) , Cao, Can (VerfasserIn) , Zhou, Yinuo (VerfasserIn) , Gavrilov, Alexey A. (VerfasserIn) , Razin, Sergey V. (VerfasserIn) , Cabrera-Orefice, Alfredo (VerfasserIn) , Wittig, Ilka (VerfasserIn) , Pullamsetti, Soni Savai (VerfasserIn) , Kurian, Leo (VerfasserIn) , Gilsbach, Ralf (VerfasserIn) , Schulz, Marcel Holger (VerfasserIn) , Đikić, Ivan (VerfasserIn) , Müller-McNicoll, Michaela (VerfasserIn) , Brandes, Ralf (VerfasserIn) , Leisegang, Matthias (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 02 January 2025
In: Nature Communications
Year: 2025, Jahrgang: 16, Pages: 1-13
ISSN:2041-1723
DOI:10.1038/s41467-024-55539-6
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-024-55539-6
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-024-55539-6
Volltext
Verfasserangaben: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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 16.01.2026
Beschreibung:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-024-55539-6

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