Multi-omic profiling following loss of SWI/SNF reveals global changes in cohesin binding and sensitivity to cohesin perturbation
Description
Raw data for Lane et al., 2025. Abstract: SWI/SNF is a family of multi-subunit chromatin remodelling complexes with diverse roles in cellular processes including transcription, replication, and repair. SWI/SNF complexes play an important role in maintaining genome stability, with over 20% of all cancers having deleterious mutations in a SWI/SNF subunit. We modelled SWI/SNF dysfunction in the widely used cell line, RPE1, both by engineering a panel of loss-of-function SWI/SNF subunit mutations, and by using small molecule treatment to acutely degrade or inhibit SWI/SNF. To analyse the functional consequences of this dysfunction, we performed transcriptomic analysis and compared this with whole cell and chromatin-bound proteomes. Strikingly, SWI/SNF-associated changes in the transcriptome correlated poorly with changes at the protein level. In addition, comparative analyses of protein dynamics revealed that both acute and chronic SWI/SNF loss led to decreased association of cohesin with chromatin. Furthermore, SWI/SNF loss resulted in cohesin mislocalisation away from regulatory elements to novel distal regions in the genome. We find that the relationship between SWI/SNF and cohesin is functionally important, and cells lacking SWI/SNF show significant sensitivity to perturbation of cohesin. Our results provide an important resource mapping the consequences of acute and chronic SWI/SNF perturbation and uncover SWI/SNF as a critical regulator of cohesin dynamics.
Files
Institutions
- Institute of Cancer ResearchLondon, London