Combinations of chromatin-remodelling factors are important for the correct balance between stem cell renewal and differentiation. On , Umberto Galderisi and colleagues describe the influence of Brg1 (the ATPase subunit of the SWI/SNF ATP-dependent chromatin-remodelling enzymes) on proliferation and differentiation of mesenchymal stem cells (MSCs). SWI/SNFs are known to regulate the cell cycle, apoptosis and cell differentiation. Now, the researchers show that forced expression of Brg1 causes cell cycle arrest, apoptosis and senescence in MSCs. The researchers show that ectopic expression of Brg1 upregulates both Rb- and p53-related pathways. Dissecting the molecular mechanisms behind these observations, they find that the apoptosis that occurs is mediated by p53, and both Rb- and p53-related pathways are required for the observed cell cycle arrest and senescence. Intriguingly, ectopic expression of Brg1 is also associated with the differentiation of adipocytes, although the authors note that – unlike other ATP-dependent chromatin-remodelling factors – Brg1 does not appear to directly regulate access to promoters of genes that encode transcription factors. Instead, it promotes differentiation when other, extrinsic factors that promote adipogenesis are added to the culture medium.
