Chromatin remodeling is essential for DNA accessibility and gene expression control in health and disease. How such a fundamental process is coordinated in a spatial and temporal manner remains unknown. The SWItch\/Sucrose Non-Fermentable (SWI\/SNF) chromatin remodeling complex is expressed in every cell type from yeast to humans and remodels chromatin genome-wide. In particular, SWI\/SNF binds lineage specific enhancers where it actively maintains open chromatin state while being able to respond dynamically to cellular signals.<\/p>\n
The mechanisms that guide SWI\/SNF to specific genomic targets have remained elusive. Here\u00a0Dr. James Alexander Oo<\/strong>\u00a0and his colleagues<\/strong><\/span>\u00a0from\u00a0Matthias Leisegang`s group\u00a0<\/strong>have demonstrated that\u00a0trans<\/em>-acting long non-coding RNAs (lncRNAs) direct the SWI\/SNF complex to cell type-specific enhancers. They performed a technique called RedChIP which allowed for the pulldown of SWI\/SNF proteins bound to both RNA and DNA. Sequencing of the SWI\/SNF-enriched RNA-DNA pinpointed exactly which lncRNA was bound to which DNA site with SWI\/SNF.<\/p>\n After the validation of interactions with techniques such as iCLIP and CUT&RUN, they perfomed a knockdown screen against the candidate lncRNAs. This led to the genome-wide redistribution of SWI\/SNF away from specific enhancers and a concomitant differential expression of spatially connected target genes.<\/p>\n These 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. Considering that SWI\/SNF is fundamental in differentiation and is mutated in 25% of cancers, a better understanding of how it is recruited in a cell type- and context-dependent manner offers huge therapeutic potential.<\/p>\n <\/p>\n Find the full article here:<\/strong><\/p>\n