Disease relevance of MYOD1

• Chicken MyoD1 (CMD1), an equivalent to the mouse MyoD1, expressed in chicken skeletal muscle (Lin, Z.-Y., Dechesne, C. A., Eldridge, J., and Paterson, B. M. (1989) Genes & Dev. 3, 986-996), was produced in Spodoptera frugiperda (Sf9) cells by Baculovirus expression vector and purified to almost homogeneity [1].
• In the current study, the avian genetic muscle weakness, low score normal (LSN), which exhibits modified myotube and sarcomere structure and a reduction in beta1 integrin expression during satellite cell differentiation, was used as a model system to further investigate the role of beta1 integrins in myogenic differentiation [2].
• Therefore, in studies on the mechanism of myogenic differentiation, we examined the expression of Mb-N3 antigen on spontaneously forming myotubes formed at 41.0 degrees C and fused myoblasts with hemagglutinating virus of Japan (HVJ, Sendai virus) disregarding programmed processes for myogenic differentiation [3].

High impact information on MYOD1

• Occupation of the extracellular matrix receptor, integrin, is a control point for myogenic differentiation [4].
• Transient expression of CMD1 in BrdU-treated myoblasts reactivates cotransfected muscle-specific promoters [5].
• The efficiency of myoblast conversion depends on the levels of CMD1 expression and suggests that the cellular concentration of CMD1 plays a role in the onset of myogenesis [5].
• Nucleotide sequence analysis and amino acid comparison define this clone, CMD1, as encoding a protein similar to mouse MyoD1 [5].
• 5-Bromodeoxyuridine (BrdU) treatment of chicken and mouse myoblasts reduces the expression of CMD1 and MyoD1, respectively, and may explain how this thymidine analog inhibits myogenesis and the activity of transfected muscle-specific promoters in BrdU-treated myoblasts [5].

Biological context of MYOD1

• Surprisingly, neither muscle-specific expression, autoregulation, or cross activation depends upon the presence of of these E-box or MEF-2 binding sites in the CMD1 promoter [6].
• E-box- and MEF-2-independent muscle-specific expression, positive autoregulation, and cross-activation of the chicken MyoD (CMD1) promoter reveal an indirect regulatory pathway [6].
• CMD1 encodes a polypeptide smaller than MyoD1, 298 versus 318 amino acids, respectively, and is 80% concordant by amino acid sequence overall [5].
• Specific mutation of the Sp1 site markedly affects transactivation by CMD1 or myogenin [7].
• Its distal half, containing a pair of E boxes (CANNTG), had been previously characterized as an enhancer responsive to CMD1 but not to c-myogenin [8].

Anatomical context of MYOD1

• The CMD1 promoter is silent in primary chick fibroblast cultures and in muscle cell cultures treated with the thymidine analog bromodeoxyuridine [6].
• We have identified the minimal region in the chicken MyoD (CMD1) promoter necessary for muscle-specific transcription in primary cultures of embryonic chicken skeletal muscle [6].
• Transient expression of CMD1 in a variety of nonmuscle cells from different germ-layer origins activates both cotransfected muscle-specific promoters and, in some cases, endogenous muscle-specific genes [5].
• We conclude that the expression of an oncogenic jun gene in myoblasts strongly inhibits myogenic differentiation, and that a highly transforming Jun protein cannot be expressed in the nuclei of differentiating myotubes, while the presence of transformation-defective variants of Jun is compatible with differentiation [9].
• Expression of myogenic differentiation and myotube formation by chick embryo myoblasts in the presence of sodium butyrate [10].

Associations of MYOD1 with chemical compounds

• Phosphoinositide turnover under basal conditions in [3H]inositol-labeled cells is faster in myoblasts than in myotubes, a finding that may in part explain the different distribution of PKc observed during the course of myogenic differentiation [11].
• Gel retardation and methylation interference assays showed that purified CMD1 bound specifically to the mouse muscle creatine kinase enhancer in combination with the in vitro translated E12 [1].
• Phosphoamino acid of CMD1 from chick primary culture of 11-day embryonic breast muscle was also serine [1].
• However, CMD1 binding alone is equally efficient when either EDTA is added in excess or dephosphorylated or bacterially expressed CMD1 is used in the assay [12].
• We also found that myogenin or CMD1 overexpression in chloramphenicol-treated myoblasts did not restore differentiation, thus indicating that an alteration in mitochondrial activity interferes with the ability of myogenic factors to induce terminal differentiation [13].

Other interactions of MYOD1

• In addition bFGF inhibits myogenic differentiation, while TGF-beta 1 and TGF-beta 2 appear to have no effect [14].
• Antibodies to the myosin heavy chains of striated muscle were used to trace myogenic differentiation in the developing face and in cultures of cells from the facial primordia of chick embryos [15].
• These results indicate that partially purified interferon has multiple effects on the process of the myogenic differentiation of chicken myoblast in vitro [16].

Analytical, diagnostic and therapeutic context of MYOD1

• Moreover, both myogenin and CMD1 mRNA levels increase after muscle denervation in chicks [17].

References