Characterization of a Muscle-specific Enhancer in Human MuSK Promoter Reveals the Essential Role of Myogenin in Controlling Activity-dependent Gene Regulation

Tang, Huibin; Veldman, Matthew B.; Goldman, Daniel

doi:10.1074/jbc.m511317200

Cited by 23 publications

(20 citation statements)

References 31 publications

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“…4 and 5). The E-box is able to bind MyoD and other muscle-specific transcription factors and is found in the promoter of several muscle-specific genes such as troponin I (4), myosin heavy chain (MHC IIB) (47), MUSK (a muscle-specific tyrosine kinase receptor) (43), and the nicotinic acetylcholine receptor (nAChR) (17). The E-box is able to bind MyoD and other muscle-specific transcription factors and is found in the promoter of several muscle-specific genes such as troponin I (4), myosin heavy chain (MHC IIB) (47), MUSK (a muscle-specific tyrosine kinase receptor) (43), and the nicotinic acetylcholine receptor (nAChR) (17).…”

Section: Discussionmentioning

confidence: 99%

Identification of Sp1 and GC-boxes as transcriptional regulators of mouse Dag1 gene promoter

Rettino

Rafanelli

Genovese

et al. 2009

American Journal of Physiology-Cell Physiology

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Dystroglycan is a widely expressed adhesion complex that anchors cells to the basement membrane and is involved in embryonic development and differentiation. Dystroglycan expression is frequently reduced in human dystrophies and malignancies, and its molecular functions are not completely understood. Several posttranslational mechanisms have been identified that regulate dystroglycan expression and/or function, while little is known about how expression of the corresponding Dag1 gene is regulated. This study aimed to clone the Dag1 gene promoter and to characterize its regulatory elements. Analysis of the mouse Dag1 gene 5'-flanking region revealed a TATA and CAAT box-lacking promoter including a GC-rich region. Transfection studies with serially deleted promoter constructs allowed us to identify a minimal promoter region containing three Specificity protein 1 (Sp1) sites and an E-box. Sp1 binding was confirmed by chromatin immunoprecipitation assay, and Sp1 downregulation reduced dystroglycan expression in muscle cells. Treatment with 5-aza-2'-deoxycytidine and/or the histone deacetylase inhibitor trichostatin A increased Dag1 mRNA expression levels in myoblasts, and methylation decreased promoter activity in vitro. Furthermore, Dag1 gene promoter methylation was reduced while its expression increased during differentiation of C(2)C(12) myoblast cells in myotubes. In conclusion, for the first time we have characterized the activity of the mouse Dag1 gene promoter, confirming a complex regulation by Sp1 transcription factor, DNA methylation, and histone acetylation, which might be relevant for a better understanding of the physiopathology of the dystroglycan complex.

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Section: Discussionmentioning

confidence: 99%

Identification of Sp1 and GC-boxes as transcriptional regulators of mouse Dag1 gene promoter

Rettino

Rafanelli

Genovese

et al. 2009

American Journal of Physiology-Cell Physiology

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“…Expression of MuSK, and thereby its degree of autoactivation, is most likely controlled at the transcriptional and posttranslational levels. As for transcription, the MuSK gene contains an E box DNA binding element for the transcription factor myogenin, which suppresses transcription of genes in extrasynaptic nuclei of adult myofibers (Tang et al, 2006), and an N box DNA binding element (Lacazette et al, 2003), which induces transcription of genes in synaptic nuclei via Ets factors, which are, in part, activated by neuregulin (Burden, 1993). The late onset expression of myogenin in embryogenesis may help to dictate the suppression of MuSK, thereby tying the topography of innervation to muscle differentiation.…”

Section: The Three “A”s In the Synaptic Achr Triumvirate - Agrin Actmentioning

confidence: 99%

Role of extracellular matrix proteins and their receptors in the development of the vertebrate neuromuscular junction

Singhal

Martin

2011

Developmental Neurobiology

123

107

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The vertebrate neuromuscular junction remains the best-studied model for understanding the mechanisms involved in synaptogenesis, due to its relatively large size, its simplicity of patterning and its unparalleled experimental accessibility. During neuromuscular development, each skeletal myofiber secretes and deposits around its extracellular surface an assemblage of extracellular matrix (ECM) proteins that ultimately form a basal lamina. This is also the case at the neuromuscular junction, where the motor nerve contributes additional factors. Before most of the current molecular components were known, it was clear that the synaptic ECM of adult skeletal muscles was unique in composition and contained factors sufficient to induce the differentiation of both pre- and postsynaptic membranes. Biochemical, genetic and microscopy studies have confirmed that agrin, laminin (221, 421, and 521), collagen IV (α3-α6), collagen XIII, perlecan and the ColQ-bound form of acetylcholinesterase are all synaptic ECM proteins with important roles in neuromuscular development. The roles of their many potential receptors and/or binding proteins has been more difficult to assess at the genetic level due to the complexity of membrane interactions with these large proteins, but roles for MuSK-LRP4 in agrin signaling and for integrins, dystroglycan, and voltage-gated calcium channels in laminin-dependent phenotypes have been identified. Synaptic extracellular matrix proteins and their receptors are involved in almost all aspects of synaptic development, including synaptic initiation, topography, ultrastructure, maturation, stability and transmission.

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“…Both these factors may be important in determining the expression of MRF target genes, because some musclespecific genes have promoters or enhancers with E-boxes that preferentially bind a particular member of the MRF family (e.g., Brennan et al, 1990;Rosenthal et al, 1990;Yutzey et al, 1990;Fujisawa-Sehara et al, 1992;Sunyer and Merlie, 1993;Tang et al, 2006), while other target genes of the MRFs are not known to exhibit preferential binding. The present study confirms that the accumulation of each MRF mRNA (accumulation of transcript being based on two factors: the rate of gene transcription and transcript stability) displays a distinctive pattern during normal fetal development (cf.…”

Section: Mrf Mrna Accumulationmentioning

confidence: 99%

Neuronal control of myogenic regulatory factor accumulation in fetal muscle

Washabaugh¹,

Ontell²,

Shand³

et al. 2007

Developmental Dynamics

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The lumbosacral spinal cords of 14.5-day gestation mice (E14.5) were ablated. The number of molecules of each of the four myogenic regulatory factor (MRF) mRNAs per nanogram of total RNA were evaluated in innervated and aneural fetal crural muscles. Accumulation of all four MRF mRNAs was affected in aneural muscle, but was never more than threefold different than in innervated muscles, considerably less than after adult denervation. The effect of the nerve varied with the MRF, the fetal age, and with the muscle (extensor digitorum longus muscle [EDL] vs. soleus muscle), with the nerve having multiple effects including down-regulation of certain MRF genes at specific periods (e.g., myoD and myogenin [E16.5-E18.5] and MRF4 in the EDL only [E18.5-E19.5]); limiting the up-regulation of certain genes, which occurred in the absence of innervation (e.g., myf-5 [E18.5-E19.5] and myogenin [E14.5-E16.5]); and even enhancing the accumulation of MRF4 mRNA (E14.5-E16.5). We hypothesize that factors other than nerve contribute to the down-regulation of myf-5 and myogenin mRNAs to adult levels. Innervation was required for the emergence of the slow, but not the fast, MRF mRNA profile at birth. MyoD, found in both the nuclear and cytoplasmic protein extracts of innervated fetal muscle, increased by ϳ5-fold in the nuclear extracts (ϳ2.5-fold in the cytoplasmic) of E19.5 aneural muscles, significantly less than the 12-fold increase found in the nuclear extract of 4-day denervated adult muscle. This increase in aneural fetal muscle was due primarily to an increased concentration of myoD in muscle lineage nuclei, rather than to the presence of additional myoD

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Characterization of a Muscle-specific Enhancer in Human MuSK Promoter Reveals the Essential Role of Myogenin in Controlling Activity-dependent Gene Regulation

Cited by 23 publications

References 31 publications

Identification of Sp1 and GC-boxes as transcriptional regulators of mouse Dag1 gene promoter

Identification of Sp1 and GC-boxes as transcriptional regulators of mouse Dag1 gene promoter

Role of extracellular matrix proteins and their receptors in the development of the vertebrate neuromuscular junction

Neuronal control of myogenic regulatory factor accumulation in fetal muscle

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