Disease relevance of MYOD1

• RESULTS: The median ratios (and interquartile ranges) of MSP-amplified GSTP1 to MYOD1 in resected benign hyperplastic prostatic tissue, intraepithelial neoplasia, and adenocarcinoma were 0 (range, 0-0.1), 1.4 (range, 0- 45.9), and 250.8 (range, 53.5-697.5), respectively; all of these values were statistically significantly different (P< .001) [1].
• Because the rhabdomyosarcoma locus maps to 11p15.5, MYOD1 is very unlikely to be the primary site of alteration in these tumors [2].
• Our results suggest that serological detection of MYOD1 promoter hypermethylation may be of potential use as a prognostic marker for discriminating cervical cancer patients at high risk for lymph node metastasis or relapse [3].
• Interestingly, pilocytic astrocytomas showed no evidence of CpG island hypermethylation, but were significantly hypomethylated, relative to control tissues, at MYOD1 [4].
• Molecular characterization of Beckwith-Wiedemann syndrome (BWS) patients with partial duplication of chromosome 11p excludes the gene MYOD1 from the BWS region [5].

Psychiatry related information on MYOD1

• Id: a negative regulator of helix-loop-helix DNA binding proteins. Control of terminal myogenic differentiation [6].

High impact information on MYOD1

• We have demonstrated previously that a combination of signals from the neural tube and the floor plate/notochord complex synergistically induce the expression of myogenic bHLH genes and myogenic differentiation markers in unspecified somites [7].
• Expression of MyoD caused irreversible withdrawal from the cell cycle and myogenic differentiation in the majority (from 60 to 90%) of cultured fibroblasts, as defined by activation of muscle-specific genes, fusion into contractile myotubes, and appearance of ultrastructurally normal sarcomagenesis in culture [8].
• When confronted with tumor cells in this assay, fibroblasts readily converted into a graded pattern of myogenic differentiation, strongest in the immediate vicinity of tumor cells [9].
• Midcapillary pericytes showed only a slight propensity for myogenic differentiation [9].
• Cell cycle exit upon myogenic differentiation [10].

Chemical compound and disease context of MYOD1

• Induction of myogenic differentiation in human rhabdomyosarcoma cells by ionising radiation, N,N-dimethylformamide and their combination [11].
• Induction of myogenic differentiation in a human rhabdomyosarcoma cell line by phenylacetate [12].
• (RS)-1-¿[3-(2-hydroxyethoxy)-1-isopropoxy]propyl¿-5-fluorouracil 3b has important potential advantages over 5-FU because of its lower toxicity and its ability to induce myogenic differentiation in rhabdomyosarcoma cells [13].
• The term "benign Triton tumor," although incorrectly applied to this lesion, should be reserved for benign, true nerve sheath neoplasms exhibiting myogenic differentiation [14].
• New acyclonucleoside-like compounds such as GR-891 have important potential advantages over 5-fluorouracil because of their lower toxicity and their ability to induce myogenic differentiation in rhabdomyosarcoma cells [15].

Biological context of MYOD1

• Rhabdomyosarcoma-associated locus and MYOD1 are syntenic but separate loci on the short arm of human chromosome 11 [2].
• We have combined physical mapping of the human locus with meiotic and physical mapping in the mouse, together with synteny homologies between the two species, to compare the physical relationship between MYOD1 and the genetically ascertained human rhabdomyosarcoma-associated locus [2].
• Further, these analyses identify two syntenic clusters of muscle-associated genes on the short arm of human chromosome 11, one in the region of rhabdomyosarcoma locus that includes IGF2 and TH and the second the tightly linked MYOD1 and LDHA loci, which have been evolutionarily conserved in homologous regions of both the mouse and the rat genomes [2].
• Methylation of MYOD1 was detected more frequently in advanced stage [3].
• Myocyte enhancer factor 2 acetylation by p300 enhances its DNA binding activity, transcriptional activity, and myogenic differentiation [16].

Anatomical context of MYOD1

• The MYOD1 locus is preferentially expressed in skeletal muscle and at higher levels in its related neoplasm, rhabdomyosarcoma [2].
• The methylation value of MYOD1 was higher with elder patients both in normal colonic mucosa (p=0.034) and in cancer tissues (p=0.0012) [17].
• In primary human muscle cells Myf-3 and Myf-4 mRNA but very little Myf-5 mRNA is expressed [18].
• These results suggest that the BMP-2-induced signals, which inhibit myogenic differentiation and induce osteoblast differentiation, are transduced via BMPR-IA in C2C12 myoblasts [19].
• Although relatively undifferentiated, cell lines derived from this tumor express myogenic regulatory factors and so may be useful models of abortive myogenic differentiation [20].

Associations of MYOD1 with chemical compounds

• Myogenic differentiation, analyzed as number of nuclei present in myotubes and expression of creatine phosphokinase and myosin heavy chain, was partly inhibited by the presence of PDGF-BB in the differentiation medium [21].
• Consistent with a role for Cdk4/Cdk6 activity as a regulator of myogenic differentiation, we observed that PD 0332991 exposure promoted morphologic changes and enhanced the expression of muscle-specific proteins in cultured myoblasts and in the Rh30 cell line [22].
• The human MYOD1 transgene is suppressed by 5-bromodeoxyuridine in mouse myoblasts [23].
• Wild-type cellular Akt effects a partial reversal of LY294002-induced inhibition of myogenic differentiation [24].
• The promoter sequence contains putative muscle growth response elements for glucocorticoid, androgen, thyroid hormone, myogenic differentiation factor 1, myocyte enhancer factor 2, peroxisome proliferator-activated receptor, and nuclear factor-kappaB [25].

Physical interactions of MYOD1

• These results suggest that some of the targets of protein phosphatases 1 and 2A may include transcription factors capable of forming AP1 complexes and that these factors may play an important role during myogenic differentiation [26].

Enzymatic interactions of MYOD1

• EXPERIMENTAL DESIGN: MGMT hypermethylation, expressed as the ratio between methylated MGMT to unmethylated MYOD1 in genomic DNA, was analyzed in normal and matching tumor tissue from 90 patients with NSCLC, and a control group of 10 patients without cancer using a methylation-specific fluorogenic Real-Time PCR (Taqman) system [27].

Regulatory relationships of MYOD1

• When introduced into C2C12 myoblasts, the nonacetylatable MEF2C inhibits myogenic differentiation [16].
• Furthermore, a constitutively active RB protein could also inhibit the growth of RD cells without inducing myogenic differentiation [28].
• These suggest that deletion of p16 gene may not only facilitate growth but also inhibit the myogenic differentiation of RD RMS cells [29].
• Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro [30].
• Muscle LIM protein (MLP) is a striated muscle-specific factor that enhances myogenic differentiation and is critical to maintaining the structural integrity of the contractile apparatus [31].

Other interactions of MYOD1

• The four human muscle regulatory helix-loop-helix proteins Myf3-Myf6 exhibit similar hetero-dimerization and DNA binding properties [32].
• Telomerase reverse transcriptase promoter regulation during myogenic differentiation of human RD rhabdomyosarcoma cells [33].
• A 2.0 kb myf3 transcript was observed in 85% of tumours, a 1.8 kb myf4 transcript was detected in 70% of tumours and a 1.7 kb myf5 transcript was observed in 55% of tumours [34].
• The DNMT3b C46359T polymorphism was associated with significantly less methylation of MYOD and MLH1 and with trends for lower methylation in each of the other CpG islands examined [35].
• Like BMP-2, TGF-beta 1 inhibited myogenic differentiation [30].

Analytical, diagnostic and therapeutic context of MYOD1

• The myf3 and the myf4 gene products are correctly translated and accumulated in the nuclei as shown by immunofluorescence analysis [36].
• Still, PCR and in situ hybridization analyses of the initial phases of cardiac and skeletal myogenic differentiation determined that VMHC1 was expressed in both progenitor populations at the initiation of myogenesis regardless of the source of myoblast or site of initial differentiation [37].
• Significantly decreased staining with two markers of myogenic differentiation, myosin in keloidal fibroblasts (P = 0.002) and desmin (P = 0.007) in normal fibroblasts, could also be detected after treatment [38].
• Our results demonstrate that UCB-derived MSCs possess a potential of skeletal myogenic differentiation and also imply that these cells could be a suitable source for skeletal muscle repair and a useful tool of muscle-related tissue engineering [39].
• In order to test the hypothesis that methylation imbalance may not be a feature of cancers where the aetiologic agent or process is known, we studied the methylation status of the myogenic genes Myf-3 and Myf-4 by Southern blotting in malignant mesothelioma, a cancer strongly associated with asbestos exposure [40].

References