| First Author | Hutchins AP | Year | 2013 |
| Journal | Nucleic Acids Res | Volume | 41 |
| Issue | 4 | Pages | 2155-70 |
| PubMed ID | 23295670 | Mgi Jnum | J:200214 |
| Mgi Id | MGI:5507891 | Doi | 10.1093/nar/gks1300 |
| Citation | Hutchins AP, et al. (2013) Distinct transcriptional regulatory modules underlie STAT3's cell type-independent and cell type-specific functions. Nucleic Acids Res 41(4):2155-70 |
| abstractText | Transcription factors (TFs) regulate gene expression by binding to short DNA sequence motifs, yet their binding specificities alone cannot explain how certain TFs drive a diversity of biological processes. In order to investigate the factors that control the functions of the pleiotropic TF STAT3, we studied its genome-wide binding patterns in four different cell types: embryonic stem cells, CD4(+) T cells, macrophages and AtT-20 cells. We describe for the first time two distinct modes of STAT3 binding. First, a small cell type-independent mode represented by a set of 35 evolutionarily conserved STAT3-binding sites that collectively regulate STAT3's own functions and cell growth. We show that STAT3 is recruited to sites with E2F1 already pre-bound before STAT3 activation. Second, a series of different transcriptional regulatory modules (TRMs) assemble around STAT3 to drive distinct transcriptional programs in the four cell types. These modules recognize cell type-specific binding sites and are associated with factors particular to each cell type. Our study illustrates the versatility of STAT3 to regulate both universal- and cell type-specific functions by means of distinct TRMs, a mechanism that might be common to other pleiotropic TFs. |
