From General to Specific

In vitro studies and work done in yeast have suggested that the transcription factor DRAP1 functions as a "general" transcriptional regulator that represses transcription by preventing the interaction of TFIIB with TBP (the TATA box-binding protein of TFIIB). Iratni et al. examined the function of DRAP1during early mouse development and found that the mutant embryo exhibited gastrulation defects consistent with increased activity of Nodal, a secreted morphogen of the transforming growth factor-β family that is the primary inducer of mesoderm during gastrulation. Nodal signaling is inhibited in the early embryo by DRAP1, most likely through its interaction with FoxH1. Thus, a factor that was previously thought to be a general transcriptional regulator displays a specific role in embryonic patterning through the regulation of Nodal's positive feedback loop, providing a mechanism for regulation of morphogen signaling. R. Iratni, Y.-T. Yan, C. Chen, J. Ding, Y. Zhang, S. M. Price, D. Reinberg, M. M. Shen, Inhibition of excess nodal signaling during mouse gastrulation by the transcriptional corepressor DRAP1. Science 298, 1996-1999 (2002). [Abstract] [Full Text]