To understand the relationship between Bptf and CBP/p300, known co-activators of the Smad transcription factors, we knocked down both Bptf and CBP/p300 using siRNA technology and monitored the activation of the Smad responsive genes Lefty1, FGF8, Gsc, T, and Cer in ES cells (Figure S22C). As in the BptfΔExon2 knockout ES cell lines we observed that each of these genes are dependent on Bptf for full activation (Figure 5B). While some genes differ in there requirement for Bptf, they are all dependent on CBP/p300 for activation (Figure 5B). Our results demonstrate that a genetic knockout and siRNA mediated knockdown of Bptf result in defects in the activation of Smad responsive genes to varying degrees. Taken together, these results indicate that Bptf, like CBP/p300, acts as a co-activator of Smad responsive genes in ES cells.