Chromatin remodelling complexes catalyse changes in chromatin structure by moving or exchanging nucleosomes to regulate transcription. The switch/sucrose non-fermentable (SWI/SNF) complex, also named Brg1/Brahma-associated factor (BAF), is a chromatin remodelling complex important during embryonic stem cell (ESC) differentiation, where it maintains the pluripotent state and is essential for developmental processes, particularly neurodevelopment. Smarce1 is a core subunit of the BAF complex and Smarce1 mutations have been found in meningiomas, a central nervous system tumour. However, how Smarce1 mutations impacts on BAF assembly and function is unclear. In this study (Kashiwagi et al., 2024), Horie and colleagues address this question by using homozygous Smarce1 mutant ESCs. They find that the absence of Smarce1 induces the dissociation of BAF components, which in turn loosens binding of histones to DNA and decreases nucleosome stability. These unstable nucleosomes persist during ESC differentiation, which impairs the characteristic formation of heterochromatin and causes abnormal mesoderm differentiation and enhanced neuronal differentiation. By using a sucrose gradient sedimentation assay, the authors show that the distribution of the BAF complex along chromatin is altered in Smarce1 mutant cells; this suggests that Smarce1 is required for the proper targeting of the BAF complex to generate chromatin structures adequate for transcriptional regulation and cellular differentiation.
