Self-renewal of human embryonic stem cells (ESCs) is promoted by http://www.selleckchem.com/products/cpi-613.html FGF and TGF beta/Activin signaling, and differentiation is promoted by BMP signaling, but how these signals regulate genes significant to your maintenance of pluripotency has been unclear. Utilizing a defined medium, we show right here that the two TGF beta and FGF signals synergize to inhibit BMP signaling; sustain expression of pluripotency-associated Kinesin genes for instance NANOG, OCT4, and SOX2; and market long-term undifferentiated proliferation of human ESCs. We also show that both TGF beta- and BMP-responsive SMADs can bind with all the NANOG proximal promoter. NANOG promoter activity is enhanced by TGF beta/Activin and FGF signaling and is decreased by BMP signaling. Mutation of putative SMAD binding components decreases NANOG promoter activity to basal levels and makes NANOG unresponsive to BMP and TGF beta signaling. These effects suggest that direct binding of TGF beta/Activin-responsive SMADs on the NANOG promoter plays an necessary function in sustaining human ESC self-renewal.