| First Author | Gualdrini F | Year | 2016 |
| Journal | Mol Cell | Volume | 64 |
| Issue | 6 | Pages | 1048-1061 |
| PubMed ID | 27867007 | Mgi Jnum | J:252206 |
| Mgi Id | MGI:6094689 | Doi | 10.1016/j.molcel.2016.10.016 |
| Citation | Gualdrini F, et al. (2016) SRF Co-factors Control the Balance between Cell Proliferation and Contractility. Mol Cell 64(6):1048-1061 |
| abstractText | The ERK-regulated ternary complex factors (TCFs) act with the transcription factor serum response factor (SRF) to activate mitogen-induced transcription. However, the extent of their involvement in the immediate-early transcriptional response, and their wider functional significance, has remained unclear. We show that, in MEFs, TCF inactivation significantly inhibits over 60% of TPA-inducible gene transcription and impairs cell proliferation. Using integrated SRF ChIP-seq and Hi-C data, we identified over 700 TCF-dependent SRF direct target genes involved in signaling, transcription, and proliferation. These also include a significant number of cytoskeletal gene targets for the Rho-regulated myocardin-related transcription factor (MRTF) SRF cofactor family. The TCFs act as general antagonists of MRTF-dependent SRF target gene expression, competing directly with the MRTFs for access to SRF. As a result, TCF-deficient MEFs exhibit hypercontractile and pro-invasive behavior. Thus, competition between TCFs and MRTFs for SRF determines the balance between antagonistic proliferative and contractile programs of gene expression. |
