[PDF][PDF] SRF co-factors control the balance between cell proliferation and contractility

F Gualdrini, C Esnault, S Horswell, A Stewart… - Molecular cell, 2016 - cell.com
F Gualdrini, C Esnault, S Horswell, A Stewart, N Matthews, R Treisman
Molecular cell, 2016cell.com
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 …
Summary
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.
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