1. Rho-actin signaling to the MRTF coactivators dominates the immediate transcriptional response to serum in fibroblasts
- Author
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Richard Treisman, Francesco Gualdrini, Cyril Esnault, Stuart Horswell, Phil East, Aengus Stewart, Nik Matthews, Lincoln's Inn Fields Laboratories, and Cancer Research UK
- Subjects
Serum ,MESH: Signal Transduction ,MESH: Period Circadian Proteins ,MESH: Circadian Clocks ,Transcription, Genetic ,genetic structures ,[SDV]Life Sciences [q-bio] ,RNA polymerase II ,Biology ,MESH: Actins ,Rho ,Transcription (biology) ,MRTF ,Gene expression ,Serum response factor ,Genetics ,Animals ,MESH: Animals ,CLOCK Proteins ,MESH: Mice ,Transcription factor ,MESH: Transcription, Genetic ,MESH: Serum ,TCF ,Fibroblasts ,MESH: CLOCK Proteins ,MESH: Mitogen-Activated Protein Kinases ,Molecular biology ,Actins ,Cell biology ,Chromatin ,MESH: Serum Response Factor ,MESH: Fibroblasts ,embryonic structures ,cardiovascular system ,biology.protein ,chromatin ,SRF ,Chromatin immunoprecipitation ,signal transduction ,Research Paper ,Developmental Biology - Abstract
International audience; The transcription factor SRF (serum response factor) recruits two families of coactivators, the MRTFs (myocardin-related transcription factors) and the TCFs (ternary complex factors), to couple gene transcription to growth factor signaling. Here we investigated the role of the SRF network in the immediate transcriptional response of fibroblasts to serum stimulation. SRF recruited its cofactors in a gene-specific manner, and virtually all MRTF binding was directed by SRF. Much of SRF DNA binding was serum-inducible, reflecting a requirement for MRTF-SRF complex formation in nucleosome displacement. We identified 960 serum-responsive SRF target genes, which were mostly MRTF-controlled, as assessed by MRTF chromatin immunoprecipitation (ChIP) combined with deep sequencing (ChIP-seq) and/or sensitivity to MRTF-linked signals. MRTF activation facilitates RNA polymerase II (Pol II) recruitment or promoter escape according to gene context. MRTF targets encode regulators of the cytoskeleton, transcription, and cell growth, underpinning the role of SRF in cytoskeletal dynamics and mechanosensing. Finally, we show that specific activation of either MRTFs or TCFs can reset the circadian clock.
- Published
- 2014
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