Master transcription factors determine cell-type-specific responses to TGF-β signaling

Authors

Alan C. Mullen, Whitehead Institute
David A. Orlando, Whitehead Institute
Jamie J. Newman, Whitehead Institute
Jakob Lovén, Whitehead Institute
Roshan M. Kumar, Whitehead Institute
Steve Bilodeau, Whitehead Institute
Jessica Reddy, Whitehead Institute
Matthew G. Guenther, Whitehead Institute
Rodney P. Dekoter, Western UniversityFollow
Richard A. Young, Whitehead Institute

Document Type

Article

Publication Date

10-28-2011

Journal

Cell

Volume

147

Issue

3

First Page

565

Last Page

576

URL with Digital Object Identifier

10.1016/j.cell.2011.08.050

Abstract

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. © 2011 Elsevier Inc.