Selective repression of myoD transcription by v-Myc prevents terminal differentiation of quail embryo myoblasts transformed by the MC29 strain of avian myelocytomatosis virus

Rocca, S. Anna La; Vannucchi, Serena; Pompili, Monica; Pinney, Deborah F.; Emerson, Charles P.; Grossi, Milena; Tatò, Franco

doi:10.1038/sj.onc.1205586

Cited by 5 publications

(7 citation statements)

References 24 publications

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“…Although there is no evidence that c-Myc and MyoD can interact directly, it is possible that each may interact through a common transcription factor. It has been reported that c-Myc induces transcriptional repression of myoD in quail myoblasts and inhibits terminal differentiation (37). This finding supports a role for the efficient control of other MyoDregulated genes, including the ␣ 7 integrin.…”

Section: Fig 7 Gel Supershift Assaysupporting

confidence: 74%

“…Of the four known members of the myogenic regulatory factor family proteins (Myf5, MyoD, myogenin, and MRF4) that are important for initiating myogenic differentiation in myoblasts (36,37), MyoD was shown to be the major effector protein that can activate ␣ 7 expression (20). Because MyoD activates gene expression by binding to the promoter region of its target genes at E-box sequence CANNTG, it may interact with multiple E-box sequences in the ␣ 7 promoter.…”

Section: Fig 7 Gel Supershift Assaymentioning

confidence: 99%

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Regulation of α7 Integrin Expression during Muscle Differentiation

Xiao

Jethanandani

Ziober

et al. 2003

Journal of Biological Chemistry

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Expression of the laminin-binding ␣ 7 integrin is tightly regulated during myogenic differentiation, reflecting required functions that range from cell motility to formation of stable myotendinous junctions. However, the exact mechanism controlling ␣ 7 expression in a tissue-and differentiation-specific manner is poorly understood. This report provides evidence that ␣ 7 gene expression during muscle differentiation is regulated by the c-Myc transcription factor. In myoblasts, ␣ 7 is expressed at basal levels, but following conversion to myotubes the expression of the integrin is strongly elevated. The increased ␣ 7 mRNA and protein levels following myogenic differentiation are inversely correlated with c-Myc expression. Transfection of myoblasts with the c-Myc transcription factor down-regulated ␣ 7 expression, whereas overexpression of Madmyc, a dominantnegative c-Myc chimera, induced elevated ␣ 7 expression. Functional analysis with site-specific deletions identified a specific double E-box sequence in the upstream promoter region (؊2.0 to ؊2.6 kb) that is responsible for c-Myc-induced suppression of ␣ 7 expression. DNA-protein binding assays and supershift analysis revealed that c-Myc forms a complex with this double E-box sequence. Our results suggest that the interaction of c-Myc with this promoter region is an important regulatory element controlling ␣ 7 integrin expression during muscle development and myotendinous junction formation.The ␣ 7 integrin is the dominant laminin-binding integrin in muscle and plays diverse roles during the different stages of development. Myoblasts and satellite cells express relatively low levels of the integrin, which promotes their rapid cell movement during development and after injury (1-4). As differentiation proceeds, the elevation of ␣ 7 expression facilitates myoblast immobilization, fusion, and terminal differentiation. In mature muscle, as the ␣ 7 -rich myotendinous junctions are formed, the muscle fiber uses extra copies of the integrin for formation of stable adhesion contacts as it inserts into the tendon. It is therefore important to understand how ␣ 7 is regulated, not only for its role in modulating cellular functions but also because defects in its expression are associated with certain types of muscular dystrophy (5, 6). Our goal in the present study was to identify regulatory promoter elements of ␣ 7 expression and understand how they cooperate to fine-tune expression in myoblasts and terminally differentiated myotubes.

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Section: Fig 7 Gel Supershift Assaysupporting

confidence: 74%

Section: Fig 7 Gel Supershift Assaymentioning

confidence: 99%

Regulation of α7 Integrin Expression during Muscle Differentiation

Xiao

Jethanandani

Ziober

et al. 2003

Journal of Biological Chemistry

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“…Taking into account the prominent influence of c‐Myc on myoblast differentiation (Denis et al, 1987; La Rocca et al, 1994), we then investigated the possibility that this proto‐oncogene could be involved in this regulation. For this purpose, we studied the influence of chloramphenicol or p43 overexpression on c‐myc expression in avian myoblasts.…”

Section: Resultsmentioning

confidence: 99%

“…In search for other targets of mitochondrial activity involved in the control of myoblast differentiation, we observed that, in contrast to c‐myc, MEF2C, and Id expressions were not significantly affected by chloramphenicol (unpublished data). Interestingly, down‐regulation of c‐Myc expression is considered as an important event involved in the induction of differentiation for numerous cell lines (Siebenlist et al, 1988; Grolli et al, 1997; Vizirianakis et al, 2002), including murine and avian myoblasts (Crescenzi et al, 1994; La Rocca et al, 1994). According to our preliminary data, we studied the influence of inhibition or stimulation of mitochondrial activity on c‐myc expression and we assessed the possible involvement of this cellular oncogene on the organelle myogenic influence.…”

mentioning

confidence: 99%

Mitochondrial activity regulates myoblast differentiation by control of c‐Myc expression

Seyer¹,

Grandemange²,

Busson³

et al. 2005

Journal Cellular Physiology

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We have previously shown that mitochondrial activity is an important regulator of myoblast differentiation, partly through processes targeting myogenin expression. Here, we investigated the possible involvement of c-myc in these processes. Inhibition of mitochondrial activity by chloramphenicol abrogated the decrease in c-myc mRNA and protein levels occurring at the onset of terminal differentiation. Conversely, stimulation of mitochondrial activity by overexpression of the T3 mitochondrial receptor (p43) down-regulated c-myc expression. In addition, c-myc overexpression mimicked the influence of mitochondrial activity inhibition on myoblast differentiation. Moreover, like chloramphenicol, c-myc overexpression strongly inhibited the myogenic influence of p43 overexpression. These data suggest that c-Myc is an important target of mitochondrial activity involved in the myogenic influence of the organelle. Lastly, we found that chloramphenicol influence is negatively related to the frequency of post-mitotic myoblasts in the culture at the onset of treatment, and cell cycle analyses demonstrated that the frequency of myoblasts in G0-G1 phase at cell confluence is increased by p43 overexpression and decreased by chloramphenicol or c-myc overexpression. These results suggest that irreversible myoblast withdrawal from the cell cycle is a target of mitochondrial activity by control of c-Myc expression.

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“…Repression of MRF genes at the transcriptional level is induced by growth factors (Vaidya et al, 1989) and oncogenes such as E1A (Caruso et al, 1993), activated ras (Lassar et al, 1989a, b;Russo et al, 1997) and v-myc (La Rocca et al, 2002). One level of inhibition of muscle differentiation by v-Src is on the expression of MyoD and myogenin in C2C12-SR1 myoblasts and of myogenin in QMb-LA29.…”

Section: Mrf Expression and Transactivation Function Are Reversibly Imentioning

confidence: 99%

v-Src inhibits myogenic differentiation by interfering with the regulatory network of muscle-specific transcriptional activators at multiple levels

et al. 2003

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The conversion of skeletal myoblasts to terminally differentiated myocytes is negatively controlled by several growth factors and oncoproteins. In this study, we have investigated the molecular mechanisms by which v-Src, a prototypic tyrosine kinase, perturbs myogenesis in primary avian myoblasts and in established murine C2C12 satellite cells. We determined the expression levels of the cell cycle regulators pRb, cyclin D1 and D3 and cyclindependent kinase inhibitors p21 and p27 in v-Srctransformed myoblasts and found that, in contrast to myogenin, they are normally modulated by differentiative cues, implying that v-Src affects myogenesis independent of cell proliferation. We then examined the levels of expression, DNA-binding ability and transcription-activation potentials of myogenic regulatory factors in transformed myoblasts and in myotubes after reactivation of a temperature-sensitive allele of v-Src. Our results reveal two distinct potential modes of repression targeted to myogenic factors. On the one hand, we show that v-Src reversibly inhibits the expression of MyoD and myogenin in C2C12 cells and of myogenin in quail myoblasts. Remarkably, these loci become resistant to activation of the kinase in the postmitotic compartment. On the other hand, we demonstrate that v-Src efficiently inhibits muscle gene expression by repressing the transcriptional activity of myogenic factors without affecting MyoD DNAbinding activity. Indeed, forced expression of MyoD and myogenin allows terminal differentiation of transformed myoblasts. Finally, we found that ectopic expression of the coactivator p300 restores transcription from extrachromosomal muscle-specific promoters.

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Selective repression of myoD transcription by v-Myc prevents terminal differentiation of quail embryo myoblasts transformed by the MC29 strain of avian myelocytomatosis virus

Cited by 5 publications

References 24 publications

Regulation of α7 Integrin Expression during Muscle Differentiation

Regulation of α7 Integrin Expression during Muscle Differentiation

Mitochondrial activity regulates myoblast differentiation by control of c‐Myc expression

v-Src inhibits myogenic differentiation by interfering with the regulatory network of muscle-specific transcriptional activators at multiple levels

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