the key intermediate in fatty acid synthesis, completely rescued proliferation. Our work supports a mechanism in which BRG1 transcriptionally promotes de novo lipid synthesis, which is necessary for maintaining high rates of proliferation. In these cells, exogenous palmitate can substitute for endogenous FASN-generated palmitate. Furthermore, BRG1 regulation of proliferation through fatty acid metabolism is breast cancer specific. We showed that key fatty acid synthesis enzymes are not upregulated by BRG1 in non-tumorigenic MCF-10A mammary epithelial cells (59). Though MCF-10A cells also require BRG1 for proliferation (84), this requirement has a different mechanism. Restoration of BRG1 expression in cells depleted for both BRG1 and BRM rescued lipid synthesis, the expression of lipogenic enzymes and cell proliferation so BRM is not required for these effects in this system.
