SWI/SNF Complex

The SWI/SNF family of chromatin-remodelling complexes, also known as BRG1/BRM-associated factor (BAF) complexes (BOX 1), are key regulators of nucleosome positioning. The SWI/SNF family chromatin remodeling complexes are multi-subunit, ATP-dependent molecular machines that slide and evict nucleosomes. They play a major role in control of the chromatin structure and regulate gene transcription in eukaryotic cells. Mutations of the human complexes are often found in cancers and neurodevelopmental disorders. Mammalian SWI/SNF complexes belong to three broad subfamilies: canonical BAF (cBAF); polybromo-associated BAF (PBAF); and the GLTSCR1 or GLTSCR1L-containing and BRD9-containing (GBAF) complex. All three complexes contain the core subunits including SMARCC1, SMARCC2, and either of the ATPases SMARCA4 or SMARCA2, but also contain numerous variable subunits that provide each of the complexes with a distinct identity.
The human SWI/SNF complexes are frequently mutated in cancer. Loss of the peripheral subunits, such as SMARCB1, PBRM1, and SMARCE1, results in formation of defective complexes, which delocalize on chromatin, deregulate gene transcription, and potentially are oncogenic. Cancer genome-sequencing studies have revealed a remarkably high prevalence of mutations in genes encoding subunits of the SWI/SNF chromatin-remodelling complexes, with nearly 25% of all cancers harbouring aberrations in one or more of these genes. Consequently, increasing research interest is being focused on understanding the prognostic and, in particular, the potential therapeutic implications of mutations in genes encoding SWI/SNF subunits^[1][2].

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