fate simply by activating ‘ESC genes’ and repressing genes involved in differentiation29–31. However, a genome-wide analysis carried out after acute depletion of BRG1 points to the esBAF complex having additional, more complex, modes of action32. Reduction of esBAF levels by RNAi-mediated knockdown of the core ATPase Brg1 causes a large number of esBAF targets to be both upregulated and downregulated32. Surprisingly, the upregulated genes include ESC-enriched genes that were already being actively transcribed, suggesting that the esBAF complex refines the expression levels of some ESC genes to keep them within the correct boundaries32. The de-repression of several pluripotency genes, including Oct4 and Nanog, in blastocysts treated with Brg1-directed short interfering RNAs30 suggests that this refinement might also occur in vivo. Nonetheless, it is unclear whether the activating or repressing functions of the esBAF complex are more crucial, and it is similarly unclear how these different outcomes of remodelling (activation versus repression) are achieved.
