Master Transcription Factors Determine Cell-Type-Specific Responses to TGF-β Signaling
Name
Mullen-2011-Master Transcription.pdf
Size
1.53 MB
Format
Adobe PDF
Checksum (MD5)
e92f7527851e90c4b7b87b97df906f76
Author(s)
Mullen, Alan C.
Orlando, David A.
Newman, Jamie Jennifer
Loven, Jakob
Kumar, Roshan M.
Bilodeau, Steve
Reddy, Jessica
Guenther, Matthew G.
DeKoter, Rodney P.
Young, Richard A.
Date Issued
October 2011
Journal
Cell
Publisher
Elsevier B.V.
Citation
Mullen, Alan C., David A. Orlando, Jamie J. Newman, Jakob Lovén, Roshan M. Kumar, Steve Bilodeau, Jessica Reddy, Matthew G. Guenther, Rodney P. DeKoter, and Richard A. Young. “Master Transcription Factors Determine Cell-Type-Specific Responses to TGF-β Signaling.” Cell 147, no. 3 (October 2011): 565–576.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cell.2011.08.050
