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Long non-coding RNAs direct the SWI/SNF complex to cell type-specific enhancersстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Oo James A., Warwick Timothy, Pálfi Katalin, Lam Frederike, McNicoll Francois, Prieto-Garcia Cristian, Günther Stefan, Cao Can, Zhou Yinuo, Gavrilov Alexey A., Razin Sergey V., Cabrera-Orefice Alfredo, Wittig Ilka, Pullamsetti Soni Savai, Kurian Leo, Gilsbach Ralf, Schulz Marcel H., Dikic Ivan, Müller-McNicoll Michaela, Brandes Ralf P., Leisegang Matthias S.
- Журнал: Nature communications
- Том: 16
- Номер: 1
- Год издания: 2025
- Издательство: Nature Pub. Group
- Местоположение издательства: United Kingdom
- Номер статьи: 131
- DOI: 10.1038/s41467-024-55539-6
- Аннотация: The coordination of chromatin remodeling is essential for DNA accessibility and gene expression control. The highly conserved and ubiquitously expres- sed 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 dyna- mically 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.
- Добавил в систему: Разин Сергей Владимирович