title: Proteomic analysis of SRF associated transcription complexes identified TFII-I as modulator of SRF function in neurons.
abstract: The serum response factor (SRF) is a neuronal activity regulated transcription factor (TF) mediating an immediate early (IEGs, e.g. cFos, Egr1) and actin cytoskeletal gene response. SRF activity is adjusted by two competing cofactor families, ternary complex factors (TCF; e.g. Elk-1) and myocardin related transcription factors (MRTF). We investigated mechanisms of SRF activation upon seizure associated neuronal activity in mice. SRF serine 103 phosphorylation or promoter binding was not obviously changed upon neuronal activation. In contrast, a SRF directed proteomic analysis uncovered established and potentially novel components of SRF associated protein complexes whose abundance was modified by neuronal activity. This included the general transcription factor TFII-I for which we provide a first functional analysis in neurons. TFII-I modulated neuronal SRF target gene expression, enhanced nerve fiber growth and modulated the shape of neuronal growth cones. Interestingly, TFII-I modulated two SRF cofactors, Elk-1 and MRTF-A, in opposite directions. TFII-I and Elk-1 co-expression enhanced SRF target gene abundance, SRF promoter binding and neurite growth, whereas TFII-I and MRTF-A resulted in opposite outcomes. In summary, we provide a first proteome wide analysis of SRF associated proteins. We characterized TFII-I as modulator of SRF activity by imposing differential impact on two SRF cofactors.
authors.affiliation: Institute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Meyer zu Reckendorf
authors.affiliation: Institute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Sofia
authors.initials: S
authors.lastname: Anastasiadou
authors.affiliation: Institute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Bachhuber
authors.affiliation: Proteome Center Tübingen, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany.
authors.forename: Mirita
authors.initials: M
authors.lastname: Franz-Wachtel
authors.affiliation: Proteome Center Tübingen, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Macek
authors.affiliation: Institute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Electronic address: bernd.knoell@uni-ulm.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Knöll
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D040901:Proteomics; D060888:Real-Time Polymerase Chain Reaction; D012640:Seizures / Q000378:metabolism; D026362:Serum Response Factor / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D014157:Transcription Factors / Q000378:metabolism; D019473:Transcription Factors, TFII / Q000378:metabolism*
chemical_list: D026362:Serum Response Factor; D014157:Transcription Factors; D019473:Transcription Factors, TFII
keywords: Growth cone; MRTF; Neuron; SRF; TCF; TFII-I