Master Transcription Factors Determine Cell-Type-Specific Responses to TGF-beta Signaling

作者：Mullen Alan C; Orlando David A; Newman Jamie J; Loven Jakob; Kumar Roshan M; Bilodeau Steve; Reddy Jessica; Guenther Matthew G; DeKoter Rodney P; Young Richard A^*

来源：Cell, 2011, 147(3): 565-576.

DOI：10.1016/j.cell.2011.08.050

Transforming growth factor beta (TGF-beta) signaling, mediated through the transcription factors Smad2 and Smad3 (Smad2/3), directs different responses in different cell types. Here we report that Smad3 co-occupies the genome with cell-type-specific master transcription factors. Thus, Smad3 occupies the genome with Oct4 in embryonic stem cells (ESCs), Myod1 in myotubes, and PU.1 in pro-B cells. We find that these master transcription factors are required for Smad3 occupancy and that TGF-beta signaling largely affects the genes bound by the master transcription factors. Furthermore, we show that induction of Myod1 in nonmuscle cells is sufficient to redirect Smad3 to Myod1 sites. We conclude that cell-type-specific master transcription factors determine the genes bound by Smad2/3 and are thus responsible for orchestrating the cell-type-specific effects of TGF-beta signaling.

• 出版日期2011-10-28