The Regulation of MyoD Gene Expression: Conserved Elements Mediate Expression in Embryonic Axial Muscle

A strong correlative pattern between MyoD gene expression and myosin heavy chain IIB (MHC IIB) gene expression exists. To test whether this correlative relationship is causative, MHC gene expression in muscles from MyoD(−/−) mice was analyzed. The MHC IIB gene was not detectable in the MyoD(−/−) diaphragm, whereas the MHC IIB protein made up 10.0 ± 1.7% of the MHC protein pool in the wild-type (WT) mouse diaphragm. Furthermore, the MHC IIA protein was not detectable in the MyoD(−/−) biceps brachii, and the MHC IIB protein was overexpressed in the masseter. To examine whether MyoD is required for the upregulation of the MHC IIB gene within slow muscle after disuse, MyoD(−/−) and WT hindlimb musculature was unweighted. MyoD(−/−) exhibited a diminished response in the upregulation of the MHC IIB mRNA within the soleus muscle as a result of the hindlimb unweighting. Collectively, these data suggest that MyoD plays a role in the MHC profile in a muscle-specific fashion.

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Estrogen receptor regulates MyoD gene expression by preventing AP-1-mediated repression

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2009.08.153 ◽

2009 ◽

Vol 389 (2) ◽

pp. 360-365 ◽

Cited By ~ 11

Author(s):

G. Pedraza-Alva ◽

J.M. Zingg ◽

A. Donda ◽

L. Pérez-Martínez

Keyword(s):

Gene Expression ◽

Estrogen Receptor ◽

Myod Gene

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Effect of Acute Aerobic Physical Activity on Skeletal Muscle MyoD Gene Expression of Wistar Rats

Majalah Kedokteran Bandung ◽

10.15395/mkb.v51n1.1665 ◽

2019 ◽

Vol 51 (1) ◽

pp. 58-62

Author(s):

Setiawan Setiawan ◽

Mochammad Aldo ◽

Julia Windi Goenadi ◽

Hanna Goenawan ◽

Yuni Susanti Pratiwi ◽

...

Keyword(s):

Gene Expression ◽

Physical Activity ◽

Skeletal Muscle ◽

Wistar Rats ◽

Myod Gene

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The Xenopus MyoD gene: an unlocalised maternal mRNA predates lineage-restricted expression in the early embryo

Development ◽

10.1242/dev.108.4.669 ◽

1990 ◽

Vol 108 (4) ◽

pp. 669-680 ◽

Cited By ~ 1

Author(s):

R.P. Harvey

Keyword(s):

Gene Expression ◽

Cultured Cells ◽

Early Response ◽

Early Embryo ◽

Mesoderm Induction ◽

Animal Pole ◽

Early Expression ◽

Inducing Factors ◽

Mesoderm Inducing Factors ◽

Myod Gene

Expression of the mouse MyoD gene appears to represent a critical point in the commitment of cultured cells to muscle. In Xenopus, myogenic commitment begins during mesoderm induction which is initiated early in development by endogenous growth factors. To study MyoD gene expression during induction, a Xenopus MyoD gene and homologous cDNAs were selected from Xenopus libraries and analysed. Two different cDNAs have been sequenced. They code for proteins closely related to each other and to mouse MyoD and are likely to be expressed from duplicated Xenopus MyoD genes. Surprisingly, MyoD mRNA is first detected during oogenesis and the maternal species is not localized exclusively to the region of the blastula fated to muscle. Zygotic MyoD mRNA accumulates slowly above maternal levels beginning at the MBT and new transcripts are localized to the somitic mesoderm. Expression outside of somites has been detected in developing heads of tailbud embryos and can be induced in blastula animal pole explants treated with mesoderm-inducing factors. The early expression of MyoD in Xenopus development suggests that it may play a part in the induction of muscle mesoderm and generally strengthens the evidence that MyoD is determinative in muscle commitment. In addition, the initiation of MyoD transcription at the MBT and its stimulation by mesoderm-inducing factors implies that MyoD gene expression is an immediate early response to mesoderm induction.

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RhoA GTPase and Serum Response Factor Control Selectively the Expression of MyoD without Affecting Myf5 in Mouse Myoblasts

Molecular Biology of the Cell ◽

10.1091/mbc.9.7.1891 ◽

1998 ◽

Vol 9 (7) ◽

pp. 1891-1902 ◽

Cited By ~ 95

Author(s):

Gilles Carnac ◽

Michael Primig ◽

Magali Kitzmann ◽

Philippe Chafey ◽

David Tuil ◽

...

Keyword(s):

Gene Expression ◽

G Proteins ◽

Transcriptional Activation ◽

Serum Response Factor ◽

Muscle Differentiation ◽

Dominant Negative ◽

Response Factor ◽

Rhoa Protein ◽

Myod Gene ◽

Serum Response

MyoD and Myf5 belong to the family of basic helix-loop-helix transcription factors that are key operators in skeletal muscle differentiation. MyoD and Myf5 genes are selectively activated during development in a time and region-specific manner and in response to different stimuli. However, molecules that specifically regulate the expression of these two genes and the pathways involved remain to be determined. We have recently shown that the serum response factor (SRF), a transcription factor involved in activation of both mitogenic response and muscle differentiation, is required for MyoD gene expression. We have investigated here whether SRF is also involved in the control of Myf5 gene expression, and the potential role of upstream regulators of SRF activity, the Rho family G-proteins including Rho, Rac, and CDC42, in the regulation of MyoD and Myf5. We show that inactivation of SRF does not alter Myf5 gene expression, whereas it causes a rapid extinction of MyoD gene expression. Furthermore, we show that RhoA, but not Rac or CDC42, is also required for the expression of MyoD. Indeed, blocking the activity of G-proteins using the general inhibitor lovastatin, or more specific antagonists of Rho proteins such as C3-transferase or dominant negative RhoA protein, resulted in a dramatic decrease of MyoD protein levels and promoter activity without any effects on Myf5 expression. We further show that RhoA-dependent transcriptional activation required functional SRF in C2 muscle cells. These data illustrate that MyoD and Myf5 are regulated by different upstream activation pathways in which MyoD expression is specifically modulated by a RhoA/SRF signaling cascade. In addition, our results establish the first link between RhoA protein activity and the expression of a key muscle regulator.

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Lactate Promotes Myoblast Differentiation and Myotube Hypertrophy via a Pathway Involving MyoD In Vitro and Enhances Muscle Regeneration In Vivo

International Journal of Molecular Sciences ◽

10.3390/ijms19113649 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3649 ◽

Cited By ~ 14

Author(s):

Sakuka Tsukamoto ◽

Ayako Shibasaki ◽

Ayano Naka ◽

Hazuki Saito ◽

Kaoruko Iida

Keyword(s):

Gene Expression ◽

Myogenic Differentiation ◽

Underlying Mechanism ◽

Myoblast Differentiation ◽

Dependent Manner ◽

Gene And Protein Expression ◽

Myotube Hypertrophy ◽

Myod Gene

Lactate is a metabolic substrate mainly produced in muscles, especially during exercise. Recently, it was reported that lactate affects myoblast differentiation; however, the obtained results are inconsistent and the in vivo effect of lactate remains unclear. Our study thus aimed to evaluate the effects of lactate on myogenic differentiation and its underlying mechanism. The differentiation of C2C12 murine myogenic cells was accelerated in the presence of lactate and, consequently, myotube hypertrophy was achieved. Gene expression analysis of myogenic regulatory factors showed significantly increased myogenic determination protein (MyoD) gene expression in lactate-treated cells compared with that in untreated ones. Moreover, lactate enhanced gene and protein expression of myosin heavy chain (MHC). In particular, lactate increased gene expression of specific MHC isotypes, MHCIIb and IId/x, in a dose-dependent manner. Using a reporter assay, we showed that lactate increased promoter activity of the MHCIIb gene and that a MyoD binding site in the promoter region was necessary for the lactate-induced increase in activity. Finally, peritoneal injection of lactate in mice resulted in enhanced regeneration and fiber hypertrophy in glycerol-induced regenerating muscles. In conclusion, physiologically high lactate concentrations modulated muscle differentiation by regulating MyoD-associated networks, thereby enhancing MHC expression and myotube hypertrophy in vitro and, potentially, in vivo.

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MyoD Distal Regulatory Region Contains an SRF Binding CArG Element Required for MyoD Expression in Skeletal Myoblasts and during Muscle Regeneration

Molecular Biology of the Cell ◽

10.1091/mbc.e02-07-0451 ◽

2003 ◽

Vol 14 (5) ◽

pp. 2151-2162 ◽

Cited By ~ 46

Author(s):

Aurore L'honore ◽

Ned J. Lamb ◽

Marie Vandromme ◽

Patric Turowski ◽

Gilles Carnac ◽

...

Keyword(s):

Gene Expression ◽

Muscle Regeneration ◽

Cell Activation ◽

Regulatory Region ◽

Mouse Muscle ◽

Skeletal Myoblasts ◽

Distal Regulatory Region ◽

Nucleotide Mutation ◽

Myod Gene ◽

Myod Expression

We show here that the distal regulatory region (DRR) of the mouse and human MyoD gene contains a conserved SRF binding CArG-like element. In electrophoretic mobility shift assays with myoblast nuclear extracts, this CArG sequence, although slightly divergent, bound two complexes containing, respectively, the transcription factor YY1 and SRF associated with the acetyltransferase CBP and members of C/EBP family. A single nucleotide mutation in the MyoD-CArG element suppressed binding of both SRF and YY1 complexes and abolished DRR enhancer activity in stably transfected myoblasts. This MyoD-CArG sequence is active in modulating endogeneous MyoD gene expression because microinjection of oligonucleotides corresponding to the MyoD-CArG sequence specifically and rapidly suppressed MyoD expression in myoblasts. In vivo, the expression of a transgenic construct comprising a minimal MyoD promoter fused to the DRR and β-galactosidase was induced with the same kinetics as MyoD during mouse muscle regeneration. In contrast induction of this reporter was no longer seen in regenerating muscle from transgenic mice carrying a mutated DRR-CArG. These results show that an SRF binding CArG element present in MyoD gene DRR is involved in the control of MyoD gene expression in skeletal myoblasts and in mature muscle satellite cell activation during muscle regeneration.

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