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• W2165997923 abstract "HomeCirculation ResearchVol. 92, No. 8Decisions, Decisions … SRF Coactivators and Smooth Muscle Myogenesis Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBDecisions, Decisions … SRF Coactivators and Smooth Muscle Myogenesis Mark W. Majesky Mark W. MajeskyMark W. Majesky From the Carolina Cardiovascular Biology Center, Departments of Medicine and Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC. Search for more papers by this author Originally published2 May 2003https://doi.org/10.1161/01.RES.0000071525.18323.4CCirculation Research. 2003;92:824–826Smooth muscle-restricted gene transcription depends on a highly conserved cis-regulatory element termed a CArG box [CC(A/T)6GG]. The CArG box binds serum response factor (SRF), an evolutionarily conserved MADS (MDM1, agamous, deficiens, SRF) domain-containing protein that is required for specification of smooth, cardiac, and skeletal muscle lineages from early mesoderm.1 SRF is a multifunctional protein that not only binds DNA but also provides docking surfaces within the conserved core MADS domain for interaction with a wide variety of accessory cofactors. Most, but not all, smooth muscle cell (SMC) marker genes examined to date require SRF interactions with pairs of CArG-like elements that often contain single G/C substitutions in the AT-rich core region. However, SRF-CArG interactions alone are not sufficient to produce the diversity of smooth muscle subtypes found within the vascular system. A report by Yoshida et al in this issue of Circulation Research confirms and extends previous work by Wang et al,2,3 Chen et al,4 and Du et al,5 suggesting that myocardin is a potent SRF-dependent coactivator for smooth muscle differentiation.6Control of SRF-Dependent Transcription by Accessory CofactorsSRF-CArG box interactions confer context-dependent and signal-responsive control of muscle-specific gene transcription (Figure). This is accomplished at multiple levels of regulation including control of SRF expression, cytoplasmic to nuclear translocation, alternative splicing, and posttranslational modifications of SRF itself. Perhaps the most important mechanism for control of CArG box-dependent transcription is the physical association of SRF with various cell-restricted and/or signal-dependent accessory factors that confer coactivator or corepressor activity via ternary complex formation. This feature of SRF-mediated transcription was first described for the 23 base pair (bp) serum response element (SRE) of the c-fos gene.7 Growth factor responsiveness of the c-fos promoter is a result of the association of SRF with a family of Ets domain-containing transcription factors called ternary complex factors (TCFs). TCFs, including Elk1, SAP1, and SAP2/Net, are targets of mitogen-activated protein (MAP) kinase signaling. Binding of TCFs to the core MADS domain of SRF depends on SRF-CArG box interactions and on weak contacts made by TCFs with GGAA/T sequences that immediately flank the c-fos SRE.8Download figureDownload PowerPointSRF accessory factors modify SRF-CArG interactions and SRF protein-protein interactions, thereby governing the decision of whether CArG-dependent target genes are expressed. These accessory factors are also targets of upstream signaling pathways mediated by Rho kinase or MAP kinase activation. Therefore, the ability of SRF-CArG interactions to respond to signals for growth or differentiation is largely due to protein-protein interactions mediated by the MADS domain of SRF binding to various SRF coactivators and corepressors.Myocardin and MRTFs Are Novel SRF CoactivatorsMyocardin is a SAP (SAF-A/B, acinus, PIAS) domain-containing protein that was discovered by Olson and colleagues during an in silico screen for genes that are selectively expressed in early cardiac development.2 Myocardin contains conserved basic, polyglutamine-rich (Q-rich), and SAP domains in the N-terminal portion of the protein and a strong transcriptional transactivation domain at the C-terminus. Wang et al2 first showed that expression of myocardin is restricted to cardiac and smooth muscle lineages in developing mouse embryos, and that it is capable of potent transactivation of CArG box-containing promoter-reporter constructs in a manner that is strictly dependent on its association with SRF. Chen et al4 showed that myocardin expression is maintained in adult aortic media and is downregulated in all cultured SMC lines examined. In fact, these authors reported that some SMC cultures expressed robust levels of SM-calponin but undetectable levels of myocardin. Likewise, Du et al5 showed that embryonic day 9.5 (E9.5) mouse aorta strongly expresses SM22α and SM α-actin with little or no detectable myocardin expression. The observations that CArG-dependent smooth muscle marker genes are expressed in cells and tissues in which myocardin mRNA is undetectable may be explained by the presence of one or more myocardin-related transcription factors (MRTFs). MRTF-A and MRTF-B were discovered by Wang et al3 on screening cDNA libraries with myocardin-related probes obtained from EST database searches with the mouse myocardin cDNA sequence. MRTF-A and MRTF-B share strong sequence homology with myocardin in the basic and Q-rich domains, which are the SRF-binding portions of the molecule. MRTF-A activated CArG-dependent SMC promoters to levels similar to that produced by myocardin, whereas MRTF-B was less effective. MRTF-A is ubiquitously expressed throughout the mouse embryo at E10.5, and at lower levels by E13.5, whereas MRTF-B is expressed in a variety of epithelial cells, enteric smooth muscle, and mesenchymal cells of the lung and olfactory tissues.3 Of course, it is also possible that initial activation of SMC marker genes in vascular development depends on one or more SRF accessory cofactors other than myocardin or MRTFs (see below). In this case, myocardin may function in the maintenance or amplification of SMC differentiation as development of the vessel wall proceeds. Regardless of the role that myocardin or MRTFs play in the initial steps of SMC differentiation from committed progenitors, downregulation of myocardin expression with a dominant-negative myocardin mutant protein or small-interfering RNA (siRNA) greatly reduced ongoing SM22α, SM α-actin, and SM-MHC promoter activity in adult aortic SMCs.5,6Myocardin Activates Smooth Muscle Genes in Non-SMCsForced expression of myocardin in non-SMCs activated SMC marker gene expression in mouse embryonic stem (ES) cells3,5 and in L6 myoblasts.4 The ability of myocardin to activate SMC reporter genes was abolished in SRF−/− ES cells and was restored upon introduction of SRF expression vectors into SRF−/− ES cells.3,5 Of particular interest is the present report by Yoshida et al.6 These authors previously developed a cell line, called A404, which represents an SMC progenitor that is present in small numbers in P19 mouse embryonal carcinoma cell lines.9 Isolation of this SMC progenitor subset was accomplished by introduction of an SM α-actin promoter/intron-driven puromycin resistance gene followed by treatment with retinoic acid (RA) plus puromycin. Of the surviving clones, one in particular exhibited rapid and extensive differentiation to SMCs upon stimulation with RA and was designated A404. While parental P19 cells do not express myocardin, undifferentiated A404 cells express low levels of myocardin, which are markedly increased along with SMC markers after stimulation with RA.6 In this system, SRF expression levels are high in undifferentiated cells and do not increase over the time course of SMC differentiation. Chromatin immunoprecipitation (ChIP) assays showed that CArG elements of SMC target genes are not accessible in undifferentiated cells. However, stimulation with RA led to an increase in SRF binding to SM α-actin and SM-MHC CArG elements within intact chromatin in differentiated cells.9 Although the effects of inhibiting myocardin expression in A404 cells were not tested, studies using dominant-negative myocardin or siRNA specific for myocardin in cultures of adult rat aortic SMCs showed that endogenous SM α-actin and SM-MHC gene expression was myocardin-dependent.6 Moreover, myocardin was found in an SRF-containing complex that forms on a 95-bp probe containing CArG-A and CArG-B elements from the SM α-actin proximal promoter when nuclear extracts from SMCs, but not endothelial cells, were used to perform electrophoretic mobility shift assays.6SRF Interacts With Multiple Transcriptional Coactivators and CorepressorsThe evolutionarily conserved MADS domain serves as a platform for binding of a diverse group of accessory proteins that control CArG-dependent transcription. In addition to myocardin and MRTFs, the SRF-MADS box can also physically interact with NK class homeodomain proteins including Nkx2.5, Nkx3.1, and Nkx3.2. Carson et al10 reported that a conserved NKE site proximal to an adjacent CArG element in the SM γ-actin promoter binds Nkx3.1 and promotes physical association with SRF via homeodomain-MADS box interactions. The combination of Nkx3.1 and SRF strongly coactivated SM γ-actin promoter activity in CV1 cells. Nishida et al11 reported that the homeodomain of Nkx3.2 and the zinc-finger basic domain of GATA6 can physically interact with the SRF-MADS box. A multiprotein complex composed of SRF, Nkx3.2, and GATA6 is correlated with strong transactivation of the chick α1-integrin promoter activity in 10T1/2 cells.11 In addition to NK homeodomains, the paired class homeodomain protein Phox1, its mouse orthologue Mhox, as well as Barx2B coassociate with SRF and increase the affinity of SRF for binding to DNA.15,16 SRF homeodomain interactions can also inhibit transcription. The homeodomain-only protein (HOP) physically interacts with the SRF-MADS domain leading to strong inhibition of CArG-dependent transcription.12 Factors that promote the interaction of SRF with critical accessory proteins are also being identified. Of particular interest in this regard is the recent identification of double LIM domain-containing cysteine-rich proteins Crp1 and Crp2 as highly efficient bridging proteins that promote assembly of SRF-GATA factor complexes and greatly potentiate CArG-dependent transcription of SMC marker genes.13 Introduction of Crp1 or Crp2, together with SRF and GATA6, induced the expression of multiple SM marker genes in 10T1/2 mesenchymal cells.13SummaryAccessory cofactors for SRF play key roles in signal-responsive control of CArG-dependent transcription.14 Myocardin is expressed in developing and adult vascular SMCs, physically associates with SRF, and greatly potentiates SRF-dependent transcription of multiple SMC marker genes.2–6 While it is tempting to speculate that myocardin will turn out to be a key factor in control of vascular SMC differentiation in vivo, it is unlikely to account for the full range of SMC differentiation phenotypes described in normal and diseased artery wall. In that regard, other SRF cofactors including MRTFs, Nkx, and paired-type homeodomain proteins, GATA factors, HOP, Barx2B, chromatin-organizing factors HMGI(Y) and SSRP1, YY1, and LIM domain-containing proteins including Crp1 and Crp2 are also likely to be involved.2–6,10–16 It will be of great interest to determine if and to what extent myocardin interacts with one or more of these SRF cofactors, whether or not myocardin is a target for posttranslational modifications by MAP kinase or rho kinase signaling pathways, and how the interplay between SRF-MADS domain-interacting proteins controls the expression of various CArG-dependent genes in the transitions between growth and differentiation characteristic of the vascular SMC in vivo.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.FootnotesCorrespondence to Mark W. Majesky, PhD, Carolina Cardiovascular Biology Center, 5109 Neurosciences Research Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. E-mail [email protected] References 1 Arsenian S, Weinhold B, Oelgeschlager M, Ruther U, Nordheim A. Serum response factor is essential for mesoderm formation during mouse embryogenesis. EMBO J. 1998; 17: 6289–6299.CrossrefMedlineGoogle Scholar2 Wang DZ, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, Krieg PA, Olson EN. Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor. Cell. 2001; 105: 851–862.CrossrefMedlineGoogle Scholar3 Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, Richardson JA, Nordheim A, Olson EN. Potentiation of serum response factor activity by a family of myocardin-related transcription factors. Proc Natl Acad Sci U S A. 2002; 99: 14855–14860.CrossrefMedlineGoogle Scholar4 Chen J, Kitchen CM, Streb JW, Miano JM. Myocardin: a component of a molecular switch for smooth muscle differentiation. J Mol Cell Cardiol. 2002; 34: 1345–1356.CrossrefMedlineGoogle Scholar5 Du KL, Ip HS, Li J, Chen M, Dandre F, Yu W, Lu MM, Owens GK, Parmacek MS. Myocardin is a critical serum response factor cofactor in the transcriptional program regulating smooth muscle cell differentiation. Mol Cell Biol. 2003; 23: 2425–2437.CrossrefMedlineGoogle Scholar6 Yoshida T, Sinha S, Dandré F, Wamhoff BR, Hoofnagle MH, Kremer BE, Wang DZ, Olson EN, Owens GK. Myocardin is a key regulator of CArG-dependent transcription of multiple smooth muscle marker genes. Circ Res. 2003; 92: 856–864.LinkGoogle Scholar7 Shaw PE, Schroter H, Nordheim A. The ability of a ternary complex to form over the serum response element correlates with serum inducibility of the human c-fos promoter. Cell. 1989; 56: 563–572.CrossrefMedlineGoogle Scholar8 Triesman R. Journey to the surface of the cell: Fos regulation and the SRE. EMBO J. 1995; 14: 4905–4913.CrossrefMedlineGoogle Scholar9 Manabe I, Owens GK. Recruitment of serum response factor and hyperacetylation of histones at smooth muscle-specific regulatory regions during differentiation of a novel P19-derived in vitro smooth muscle differentiation system. Circ Res. 2001; 88: 1127–1134.CrossrefMedlineGoogle Scholar10 Carson JA, Fillmore RA, Schwartz RJ, Zimmer WE. The smooth muscle γ-actin gene promoter is a molecular target for the mouse bagpipe homologue, mNkx3–1, and serum response factor. J Biol Chem. 2000; 275: 39061–39072.CrossrefMedlineGoogle Scholar11 Nishida Y, Nakamura M, Mori S, Takahashi M, Ohkawa Y, Tadokoro S, Yoshida K, Hiwada K, Hayashi K, Sobue K. A triad of serum response factor and the GATA and NK families governs the transcription of smooth and cardiac muscle genes. J Biol Chem. 2002; 277: 7308–7317.CrossrefMedlineGoogle Scholar12 Shin CH, Liu ZP, Passier R, Zhang CL, Wang DZ, Harris TM, Yamagishi H, Richardson JA, Childs G, Olson EN. Modulation of cardiac growth and development by HOP, an unusual homeodomain protein. Cell. 2002; 110: 725–735.CrossrefMedlineGoogle Scholar13 Chang DF, Belaguli NS, Iyer D, Roberts WB, Wu SP, Dong XR, Marx JG, Moore MS, Beckerle MC, Majesky MW, Schwartz RJ. Cysteine-rich LIM-only proteins Crp1, and CRP2 are potent smooth muscle differentiation cofactors. Dev Cell. 2003; 4: 107–118.CrossrefMedlineGoogle Scholar14 Reecy JM, Belaguli NS, Schwartz RJ. Serum response factor-Nk homeodomain factor interactions: role in cardiac development. In: Harvey R, Rosenthal N, eds. Heart Development. New York, NY: Academic Press; 1998:273–290.Google Scholar15 Herring BP, Kriegel AM, Hoggatt AM. Identification of Barx2b, a serum response factor-associated homeodomain protein. J Biol Chem. 2001; 276: 14482–14489.CrossrefMedlineGoogle Scholar16 Hautmann MB, Thompson MM, Swartz EA, Olson EN, Owens GK. Angiotensin II–induced stimulation of smooth muscle α-actin expression by serum response factor and the homeodomain transcription factor MHox. Circ Res. 1997; 81: 600–610.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByXiao Q, Pepe A, Wang G, Luo Z, Zhang L, Zeng L, Zhang Z, Hu Y, Ye S and Xu Q (2012) Nrf3-Pla2g7 Interaction Plays an Essential Role in Smooth Muscle Differentiation From Stem Cells, Arteriosclerosis, Thrombosis, and Vascular Biology, 32:3, (730-744), Online publication date: 1-Mar-2012. Alexander M and Owens G (2012) Epigenetic Control of Smooth Muscle Cell Differentiation and Phenotypic Switching in Vascular Development and Disease, Annual Review of Physiology, 10.1146/annurev-physiol-012110-142315, 74:1, (13-40), Online publication date: 17-Mar-2012. Singh S, Robinson M, Nahi F, Coley B, Robinson M, Bates C, Kornacker K and McHugh K (2007) Identification of a Unique Transgenic Mouse Line That Develops Megabladder, Obstructive Uropathy, and Renal Dysfunction, Journal of the American Society of Nephrology, 10.1681/ASN.2006040405, 18:2, (461-471), Online publication date: 1-Feb-2007. Li J, Shiroyanagi Y, Lin G, Haqq C, Lin C, Lue T, Willingham E and Baskin L (2006) Serum response factor, its cofactors, and epithelial–mesenchymal signaling in urinary bladder smooth muscle formation, Differentiation, 10.1111/j.1432-0436.2006.00057.x, 74:1, (30-39), Online publication date: 1-Feb-2006. Callis T, Cao D and Wang D (2005) Bone Morphogenetic Protein Signaling Modulates Myocardin Transactivation of Cardiac Genes, Circulation Research, 97:10, (992-1000), Online publication date: 11-Nov-2005. Wang S, Elder P, Zheng Y, Strauch A and Kelm R (2005) Cell Cycle-mediated Regulation of Smooth Muscle α-Actin Gene Transcription in Fibroblasts and Vascular Smooth Muscle Cells Involves Multiple Adenovirus E1A-interacting Cofactors, Journal of Biological Chemistry, 10.1074/jbc.M409506200, 280:7, (6204-6214), Online publication date: 1-Feb-2005. Tomanek R (2005) Formation of the coronary vasculature during development, Angiogenesis, 10.1007/s10456-005-9014-9, 8:3, (273-284), Online publication date: 1-Dec-2005. Mulvihill E, Jaeger J, Sengupta R, Ruzzo W, Reimer C, Lukito S and Schwartz S (2004) Atherosclerotic Plaque Smooth Muscle Cells Have a Distinct Phenotype, Arteriosclerosis, Thrombosis, and Vascular Biology, 24:7, (1283-1289), Online publication date: 1-Jul-2004. Wang D and Olson E (2004) Control of smooth muscle development by the myocardin family of transcriptional coactivators, Current Opinion in Genetics & Development, 10.1016/j.gde.2004.08.003, 14:5, (558-566), Online publication date: 1-Oct-2004. Cen B, Selvaraj A and Prywes R (2004) Myocardin/MKL family of SRF coactivators: Key regulators of immediate early and muscle specific gene expression, Journal of Cellular Biochemistry, 10.1002/jcb.20199, 93:1, (74-82), Online publication date: 1-Sep-2004. Owens G, Kumar M and Wamhoff B (2004) Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease, Physiological Reviews, 10.1152/physrev.00041.2003, 84:3, (767-801), Online publication date: 1-Jul-2004. Jakkaraju S, Zhe X and Schuger L (2003) Role of Stretch in Activation of Smooth Muscle Cell Lineage, Trends in Cardiovascular Medicine, 10.1016/j.tcm.2003.08.004, 13:8, (330-335), Online publication date: 1-Nov-2003. Kelm R, Wang S, Polikandriotis J and Strauch A (2003) Structure/Function Analysis of Mouse Purβ, a Single-stranded DNA-binding Repressor of Vascular Smooth Muscle α-Actin Gene Transcription, Journal of Biological Chemistry, 10.1074/jbc.M306163200, 278:40, (38749-38757), Online publication date: 1-Oct-2003. May 2, 2003Vol 92, Issue 8 Advertisement Article InformationMetrics https://doi.org/10.1161/01.RES.0000071525.18323.4CPMID: 12730127 Originally publishedMay 2, 2003 Keywordsdifferentiationsignaling pathwayssmooth muscle cellstranscriptionPDF download Advertisement" @default.
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