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

By Alan C. Mullen, David A. Orlando, J. Newman, Jakob Lovén, Roshan M. Kumar, S. Bilodeau, J. Reddy, M. Guenther, R. DeKoter, Richard A. Young. Cell, 2011

613 citations recorded by the source corpus.

SUMMARY 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 (ES) cells, 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 non-muscle cells is sufficient to re-direct 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/aed94689bca9ce9c2aaca1f9693c301e1be007cc

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Citations in the corpus

Sequence and chromatin determinants of cell-type–specific transcription factor binding (2012, background): “Naturally, proximal cofactors can also influence binding through recruitment and chromatin reorganization (e.g., Mullen et al. 2011); however, the factors in our analysis that are significantly enriched in cell-type–specific proximal binding sites of cofactors are better predicted by DNase…”
Transcriptional Addiction in Cancer (2017, neutral): “Dysregulation of signaling pathways is a common feature of cancer cells; a dysregulated signaling TF can profoundly change the gene expression program through its binding to enhancers occupied by master TFs (Figure 4A) (Mullen et al., 2011; Trompouki et al., 2011), and dysregulated signaling can eve”
The Sox Family of Transcription Factors: Versatile Regulators of Stem and Progenitor Cell Fate (2013, neutral): “In cultured pluripotent ESCs, Sox2 targets are co-occupied by Smad1 and Smad3 proteins, the downstream effectors of Tgf-b signaling that are essential for self-renewal (Chen et al., 2008; Mullen et al., 2011).”
Latent enhancers activated by stimulation in differentiated cells. (2013, neutral): “Transforming growth factor beta (TGFb) stimulation of different cell types resulted in the recruitment of Smad2/3 to distinct sets of regulatory elements determined by cell-type-specific TFs (Mullen et al., 2011).”
The Cell-Cycle State of Stem Cells Determines Cell Fate Propensity (2014, neutral): “However, Activin/Nodal signaling is also necessary for endoderm differentiation and achieves these apparent contradictory functions by controlling divergent transcriptional networks in pluripotent cells and during endoderm specification (Brown et al., 2011; Mullen et al., 2011).”
Adaptive thermogenesis in adipocytes: is beige the new brown? (2013, background): “TGF-b and its related proteins play an important role in regulating growth, development, and cell fate commitment in many cell types (Chen et al. 2004; Mullen et al. 2011).”
Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription (2013, background): “As a consequence, widely expressed signal-dependent transcription factors are localized to cell-specific enhancers, resulting in cell-specific transcriptional responses (Barish et al., 2010; Biddie et al., 2011; Heinz et al., 2010; Lefterova et al., 2010; Mullen et al., 2011; Nielsen et al., 2008; T”