Master transcription factors determine cell-type-specific responses to TGF-β signaling.
Transforming growth factor beta (TGF-β) 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-β 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-β signaling.
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Alan C
AC
Mullen
David A
DA
Orlando
Jamie J
JJ
Newman
Jakob
J
Lovén
Roshan M
RM
Kumar
Steve
S
Bilodeau
Jessica
J
Reddy
Matthew G
MG
Guenther
Rodney P
RP
DeKoter
Richard A
RA
Young
D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells; D004742:Enhancer Elements, Genetic; D006801:Humans; D051379:Mice; D017570:MyoD Protein / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C494174:Pou5f1 protein, mouse; C497790:SMAD3 protein, human; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta