Separable Regulatory Elements Governing
            <i>myogenin</i>
            Transcription in Mouse Embryogenesis

Cheng, Tse Chang; Wallace, Mia; Merlie, John P.; Olson, Eric N.

doi:10.1126/science.8392225

Cited by 239 publications

(156 citation statements)

References 29 publications

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“…To understand mechanistically how OSM inhibits myoblast differentiation, we first examined the expression levels of MEF2 and MyoD that are known to be involved in regulating myogenin gene expression [54,55]. While OSM did not affect the expression of MyoD, it clearly reduced the expression of MEF2 in both primary myoblasts and C2C12 cells ( Figure 4A).…”

Section: Osm Reduced the Expression Of Mef2a Inhibited The Transcripmentioning

confidence: 99%

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Oncostatin M inhibits myoblast differentiation and regulates muscle regeneration

Xiao

Wang

et al. 2010

Cell Res

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Oncostatin M (OSM) is a cytokine of the interleukin-6 family and plays important roles during inflammation. However, its roles in myoblast differentiation and muscle regeneration remain unexplored. We show here that OSM potently inhibited myoblast differentiation mainly by activating the JAK1/STAT1/STAT3 pathway. OSM downregulated myocyte enhancer-binding factor 2A (MEF2A), upregulated the expression of Id1 and Id2, and inhibited the transcriptional activity of MyoD and MEF2. In addition, OSM also enhanced the expression of STAT3 and OSM receptor, which constituted a positive feedback loop to further amplify OSM-induced signaling. Moreover, we found that STAT1 physically associated with MEF2 and repressed its transcriptional activity, which could account for the OSM-mediated repression of MEF2. Although undetectable in normal muscles in vivo, OSM was rapidly induced on muscle injury and then promptly downregulated just before the majority of myoblasts differentiate. Prolonged expression of OSM in muscles compromised the regeneration process without affecting myoblast proliferation, suggesting that OSM functions to prevent proliferating myoblasts from premature differentiation during the early phase of muscle regeneration.

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Section: Osm Reduced the Expression Of Mef2a Inhibited The Transcripmentioning

confidence: 99%

“…This prompted us to test whether STAT1 could also physically interact with key transcription factors (e.g., MEF2 and MyoD) involved in regulating myogenin gene expression [54,55].…”

Section: Fang Xiao Et Al 355mentioning

confidence: 99%

Oncostatin M inhibits myoblast differentiation and regulates muscle regeneration

Xiao

Wang

et al. 2010

Cell Res

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“…The DNA-protein complex was resolved in a 6% polyacrylamide gel, and then electroblotted onto a Nylon membrane and UV-crosslinked. The blot was then blocked and incubated with anti-DIG antibody conjugated with alkaline phosphatase at room temperature for 30 min, washed, subjected to chemiluminescent detection with CSPD (disodium 3-(4-methoxyspiro{1,2-dioxetane-3,2′-(5′-chloro)tricyclo[3.3.1.1 3,7 ]decan}-4-yl)phenyl phosphate) as the substrate, and exposed to an X-ray film. CpG methylation of the probe was catalyzed by M.SssI as described above.…”

Section: Electrophoretic Mobility Gel Shift Assay (Emsa)mentioning

confidence: 99%

“…Myog transcription is controlled by a 1.5-kb 5′-regulatory region (nucleotides −1 565 to +18), which is sufficient to recapitulate the major features of Myog expression during embryonic and fetal development [7]. Cumulative evidence indicates that the promoter region (−184 to +18) is indispensable for Myog expression [8,9].…”

Section: Introductionmentioning

confidence: 99%

The methyl-CpG-binding protein CIBZ suppresses myogenic differentiation by directly inhibiting myogenin expression

et al. 2011

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Postnatal growth and regeneration of skeletal muscle are carried out mainly by satellite cells, which, upon stimulation, begin to express myogenin (Myog), the critical determinant of myogenic differentiation. DNA methylation status has been associated with the expression of Myog, but the causative mechanism remains almost unknown. Here, we report that the level of CIBZ, a methyl-CpG-binding protein, decreases upon myogenic differentiation of satellitederived C2C12 cells, and during skeletal muscle regeneration in mice. We present data showing that the loss of CIBZ promotes myogenic differentiation, whereas exogenous expression of CIBZ impairs it, in cultured cells. CIBZ binds to a Myog promoter-proximal region and inhibits Myog transcription in a methylation-dependent manner. These data suggest that the suppression of myogenic differentiation by CIBZ is dependent, at least in part, on the regulation of Myog. Our data show that the methylation status of this proximal Myog promoter inversely correlates with Myog transcription in cells and tissues, and during postnatal growth of skeletal muscle. Notably, induction of Myog transcription by CIBZ suppression is independent of the demethylation of CpG sites in the Myog promoter. These observations provide the first reported molecular mechanism illustrating how Myog transcription is coordinately regulated by a methyl-CpG-binding protein and the methylation status of the proximal Myog promoter.

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“…The myogenin promoter, for example, contains a MEF2 site required for high level transcription ex vivo in cultured muscle cells (Edmondson et al, 1992;Buchberger et al, 1994) and in vivo in the limb buds and somites of transgenic mice (Cheng et al, 1993;Yee and Rigby, 1993). MEF2 is also crucial to MRF4 gene expression.…”

Section: Cross-regulation Between Mef2 and Myogenic Bhlh Expressionmentioning

confidence: 99%

Identification of a New Hybrid Serum Response Factor and Myocyte Enhancer Factor 2-binding Element in MyoD Enhancer Required for MyoD Expression during Myogenesis

L’honoré

Rana

Arsic

et al. 2007

MBoC

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MyoD is a critical myogenic factor induced rapidly upon activation of quiescent satellite cells, and required for their differentiation during muscle regeneration. One of the two enhancers of MyoD, the distal regulatory region, is essential for MyoD expression in postnatal muscle. This enhancer contains a functional divergent serum response factor (SRF)-binding CArG element required for MyoD expression during myoblast growth and muscle regeneration in vivo. Electrophoretic mobility shift assay, chromatin immunoprecipitation, and microinjection analyses show this element is a hybrid SRF-and MEF2 Binding (SMB) sequence where myocyte enhancer factor 2 (MEF2) complexes can compete out binding of SRF at the onset of differentiation. As cells differentiate into postmitotic myotubes, MyoD expression no longer requires SRF but instead MEF2 binding to this dual-specificity element. As such, the MyoD enhancer SMB element is the site for a molecular relay where MyoD expression is first initiated in activated satellite cells in an SRF-dependent manner and then increased and maintained by MEF2 binding in differentiated myotubes. Therefore, SMB is a DNA element with dual and stage-specific binding activity, which modulates the effects of regulatory proteins critical in controlling the balance between proliferation and differentiation. INTRODUCTIONSkeletal muscle repair is fulfilled by satellite cells, quiescent myogenic progenitors located between the basement membrane and myofibers in both growing and mature muscle (Mauro, 1961;Schultz et al., 1978;Muir et al., 1965;Bischoff and Heintz 1994;Yablonka-Reuveni, 1995). They undergo mitogenic activation in response to exercise or damageinduced signals proliferate, differentiate, and fuse into preexisting or newly formed myofibers during muscle regeneration (Grounds and Yablonka-Reuveni, 1993;Schultz and McCormick, 1994).Among basic helix-loop-helix (bHLH) myogenic regulatory factors (MRFs), MyoD is the earliest to be induced and detected both in vivo upon muscle regeneration with activation of satellite cells and in ex vivo in cell lines derived from such precursors (Fü tchbauer and Westphal, 1992;Grounds et al., 1992). Indeed, after isolation, activated satellite cells enter the cell cycle and express MyoD concomitantly with proliferating cell nuclear antigen (Smith et al., 1994;Yablonka-Reuveni and Rivera, 1994). This finding suggested a possible role for MyoD during satellite cell activation in regeneration (Yablonka-Reuveni and Rivera, 1994;Yablonka-Reuveni et al., 1999). In agreement with this, we have reported an early induction of MyoD 4 -6 h after entry of quiescent myoblasts into the cell cycle . In addition, muscles from MyoDϪ/Ϫ mutant mice are severely deficient in regenerative capacity after injury, supporting an essential role of MyoD in adult muscle (Megeney et al., 1996). Both in vivo and ex vivo studies using isolated myofibers and primary cultured myoblasts from MyoDϪ/Ϫ mice show that without MyoD, satellite cells undergo enhanced self-renewal rather than giving ...

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Separable Regulatory Elements Governing myogenin Transcription in Mouse Embryogenesis

Cited by 239 publications

References 29 publications

Oncostatin M inhibits myoblast differentiation and regulates muscle regeneration

Oncostatin M inhibits myoblast differentiation and regulates muscle regeneration

The methyl-CpG-binding protein CIBZ suppresses myogenic differentiation by directly inhibiting myogenin expression

Identification of a New Hybrid Serum Response Factor and Myocyte Enhancer Factor 2-binding Element in MyoD Enhancer Required for MyoD Expression during Myogenesis

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