Because Bptf has been associated with the NURF complex, a known regulator of transcription, the data suggests that Bptf is required for the expression of gene targets in the developing VE and DVE. In support of this hypothesis, we showed that Bptf is required for the regulation of endogenous promoters and Smad responsive promoter elements in ES, P19 and MCF10CA1 cells in tissue culture. Smad-dependent gene targets include those essential for cell proliferation (p21) and those essential for DVE function (Cer1, Lefty1) and primitive streak (T, Fgf8, Gsc). Moreover, pulldown assays showed that components of the NURF complex have direct interactions with the Smad transcription factors and it is recruited to the promoters of Smad regulated genes under conditions of activation. Taken together, our data suggest that Bptf can directly regulate Smad regulated genes, likely through the functions of the NURF remodeling complex, via recruitment by the Smad transcription factors (It is also possible that other as yet unidentified Bptf-containing complexes distinct from NURF function in this pathway). To address the possibility that the effects on the Nodal/Smad pathway are
