Serum Response Factor and Protein-Mediated DNA Bending Contribute to Transcription of the Dystrophin Muscle-Specific Promoter

Galvagni, Federico; Lestingi, Marta; Cartocci, Elena; Oliviero, Salvatore

doi:10.1128/mcb.17.3.1731

Cited by 27 publications

(26 citation statements)

References 51 publications

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“…Another factor capable of binding to the same CArG box DNA-binding site as SRF, Yin-Yang 1, is highly expressed in MB and is displaced from muscle structural gene promoters during myogenic differentiation. 27 Our findings suggest that miR-199a-5p transcription, similar to what has been shown for other SRF-regulated miRNAs, is likewise repressed by YY1 expression levels. 28 Interestingly, miR-199a-5p expression is also induced in interstitial skeletal muscle side population cells but absent in MSCs.…”

Section: Discussionsupporting

confidence: 81%

MicroRNA-199a is induced in dystrophic muscle and affects WNT signaling, cell proliferation, and myogenic differentiation

et al. 2013

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In patients with Duchenne muscular dystrophy (DMD), the absence of a functional dystrophin protein results in sarcolemmal instability, abnormal calcium signaling, cardiomyopathy, and skeletal muscle degeneration. Using the dystrophin-deficient sapje zebrafish model, we have identified microRNAs (miRNAs) that, in comparison to our previous findings in human DMD muscle biopsies, are uniquely dysregulated in dystrophic muscle across vertebrate species. MiR-199a-5p is dysregulated in dystrophindeficient zebrafish, mdx 5cv mice, and human muscle biopsies. MiR-199a-5p mature miRNA sequences are transcribed from stem loop precursor miRNAs that are found within the introns of the dynamin-2 and dynamin-3 loci. The miR-199a-2 stem loop precursor transcript that gives rise to the miR-199a-5p mature transcript was found to be elevated in human dystrophic muscle. The levels of expression of miR-199a-5p are regulated in a serum response factor (SRF)-dependent manner along with myocardin-related transcription factors. Inhibition of SRF-signaling reduces miR-199a-5p transcript levels during myogenic differentiation. Manipulation of miR-199a-5p expression in human primary myoblasts and myotubes resulted in dramatic changes in cellular size, proliferation, and differentiation. MiR-199a-5p targets several myogenic cell proliferation and differentiation regulatory factors within the WNT signaling pathway, including FZD4, JAG1, and WNT2. Overexpression of miR-199a-5p in the muscles of transgenic zebrafish resulted in abnormal myofiber disruption and sarcolemmal membrane detachment, pericardial edema, and lethality. Together, these studies identify miR-199a-5p as a potential regulator of myogenesis through suppression of WNT-signaling factors that act to balance myogenic cell proliferation and differentiation.

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Section: Discussionsupporting

confidence: 81%

MicroRNA-199a is induced in dystrophic muscle and affects WNT signaling, cell proliferation, and myogenic differentiation

et al. 2013

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“…Wild-type and Fosl1 knockout embryonic stem cells (ESC) (11) were grown and differentiated as previously described (26). Human umbilical vein endothelial cells (HUVEC) were grown on gelatin-coated surfaces in M199 medium (Gibco) supplemented with 20% fetal bovine serum (FBS), 50 U/ml penicillin-streptomycin, 10 U/ml heparin, and 100 g/ml brain extract and filtered through a 0.22-m-pore-size sterile filter (SCGPU05RE, Stericup-GP Filter Unit; Millipore).…”

Section: Methodsmentioning

confidence: 99%

FOSL1 Controls the Assembly of Endothelial Cells into Capillary Tubes by Direct Repression of αv and β3 Integrin Transcription

Evellin

Galvagni

Zippo

et al. 2013

Molecular and Cellular Biology

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e To form three-dimensional capillary tubes, endothelial cells must establish contacts with the extracellular matrix that provides signals for their proliferation, migration, and differentiation. The transcription factor Fosl1 plays a key role in the vasculogenic and angiogenic processes as Fosl1 knockout embryos die with vascular defects in extraembryonic tissues. Here, we show that Fosl1 ؊/؊ embryonic stem cells differentiate into endothelial cells but fail to correctly assemble into primitive capillaries and to form tube-like structures. FOSL1 silencing affects in vitro angiogenesis, increases cell adhesion, and decreases cell mobility of primary human endothelial cells (HUVEC). We further show that FOSL1 is a repressor of ␣v and ␤3 integrin expression and that the down-modulation of ␣v␤3 rescues the angiogenic phenotype in FOSL1-silenced HUVEC, while the ectopic expression of ␣v␤3 alone reproduces the phenotypic alterations induced by FOSL1 knockdown. FOSL1 represses the transcription of both ␣v and ␤3 integrin genes by binding together with JunD to their proximal promoter via the transcription factor SP1. These data suggest that FOSL1-dependent negative regulation of ␣v␤3 expression on endothelial cells is required for endothelial assembly into vessel structures. V asculogenesis and angiogenesis are complex processes that, in response to angiogenic stimuli initiated by growth factors, result in a highly organized sequence of events, including cellular proliferation, migration, and formation of primitive endothelial tubes. During these processes endothelial cells (ECs) must proliferate, migrate, and establish highly dynamic cell-cell contacts and interactions with the extracellular matrix (ECM).Adhesion of endothelial cells with the ECM is mediated by integrins, which have been shown to be required during the vasculogenic and angiogenic processes (1). Mice null for ␣v die in utero showing vasculature abnormalities in the placenta (2), and neutralizing antibodies to integrin ␣v␤3 lead to abnormal vessel structures (3). The interaction of endothelial cells with the ECM is essential for endothelial cell proliferation, migration, and survival (4) and is required for tissue organization and differentiation. Moreover, upon interaction with the ECM, integrins form complexes with angiogenic receptors, contributing to their activation (5-10).Fosl1 (Fos-like 1; also named Fra1) knockout mice die between embryonic day 10.0 (E10.0) and E10.5 showing abnormal yolk sacs with placentas that are largely avascular (11).Fosl1 is an early gene that belongs to the activator protein 1 (AP-1) family of dimeric transcription factor genes (12). Fosl1 regulation is mediated by an intronic enhancer, which contains an AP-1 consensus and an E-box element next to each other (13-15).Fos proteins, including Fosl1, bind to the DNA, forming heterodimers with Jun proteins although they cannot homodimerize or heterodimerize with ATF proteins. Fosl1 lacks a transactivation domain. Therefore, its contribution to AP-1-dependent transcription dep...

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“…This DNA sequence resembles a serum responsive element (Galvagni et al, 1997;Li et al, 2005) or more likely a hybrid serum responsive factor and MEF2 binding element (L'Honore et al, 2007). The sequence is clearly critical to AChE transcriptional activation, because scrambling the DNA sequence through this region ablates AChE activity (Fig.…”

Section: Control Of Hematopoietic Expressionmentioning

confidence: 99%

Acetylcholinesterase Expression in Muscle Is Specifically Controlled by a Promoter-Selective Enhancesome in the First Intron

Camp¹,

Jaco²,

Zhang³

et al. 2008

J. Neurosci.

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Mammalian acetylcholinesterase (AChE) gene expression is exquisitely regulated in target tissues and cells during differentiation. An intron located between the first and second exons governs a ϳ100-fold increase in AChE expression during myoblast to myotube differentiation in C2C12 cells. Regulation is confined to 255 bp of evolutionarily conserved sequence containing functional transcription factor consensus motifs that indirectly interact with the endogenous promoter. To examine control in vivo, this region was deleted by homologous recombination. The knock-out mouse is virtually devoid of AChE activity and its encoding mRNA in skeletal muscle, yet activities in brain and spinal cord innervating skeletal muscle are unaltered. The transcription factors MyoD and myocyte enhancer factor-2 appear to be responsible for muscle regulation. Selective control of AChE expression by this region is also found in hematopoietic lineages. Expression patterns in muscle and CNS neurons establish that virtually all AChE activity at the mammalian neuromuscular junction arises from skeletal muscle rather than from biosynthesis in the motoneuron cell body and axoplasmic transport.

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Serum Response Factor and Protein-Mediated DNA Bending Contribute to Transcription of the Dystrophin Muscle-Specific Promoter

Cited by 27 publications

References 51 publications

MicroRNA-199a is induced in dystrophic muscle and affects WNT signaling, cell proliferation, and myogenic differentiation

MicroRNA-199a is induced in dystrophic muscle and affects WNT signaling, cell proliferation, and myogenic differentiation

FOSL1 Controls the Assembly of Endothelial Cells into Capillary Tubes by Direct Repression of αv and β3 Integrin Transcription

Acetylcholinesterase Expression in Muscle Is Specifically Controlled by a Promoter-Selective Enhancesome in the First Intron

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