Disease relevance of Myog

• We showed that hypoxia reversibly inhibited MyoD, Myf5, and myogenin expression [1].
• In mdx mice the two genes were expressed at reasonably high levels in parallel with the active regenerating process, whereas in dy mice MyoD and myogenin expressions decreased as fibrosis progressed [2].
• Immunohistochemical detection of myogenin and p21 in methylcholanthrene-induced mouse rhabdomyosarcomas [3].
• These sarcomas were investigated using a panel of immunohistochemistry and special stains consisting of desmin, smooth muscle actin (SMA), myogenin, S100, mouse macrophages, phosphotungstic acid haematoxylin (PTAH) and Masson's trichrome (MT) [4].
• Mutagenesis shows that this conserved MyoD/myogenin site is necessary for full promoter activity in both myoblasts and neuroblastoma cells [5].

Psychiatry related information on Myog

• Northern blot analysis showed that impaired differentiation was associated with delayed up-regulation of MyoD and myogenin and delayed down-regulation of Id, a dominant negative inhibitor of differentiation [6].

High impact information on Myog

• In the absence of MLP, induced C2 cells express myogenin but fail to exit from the cell cycle and to differentiate [7].
• Although NFB cells express myogenin and Myf-5 transcripts, the activity of these regulators is also repressed:myogenesis is not induced in 10T1/2 fibroblasts and is repressed in L6 muscle cells upon fusion with NFB cells [8].
• Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD [9].
• Myogenin is absent in undifferentiated cells, peaks, and then declines following a stimulus to differentiate, and is overexpressed in myoblasts selected with 5-bromodeoxyuridine for the overproduction of factors that regulate the decision to differentiate [9].
• Transfection of myogenin into the mesenchymal cell line C3H10T1/2 produces cells expressing muscle-specific markers [9].

Biological context of Myog

• We used a combination of genome-wide and promoter-specific DNA binding and expression analyses to assess the functional roles of Myod and Myog in regulating the program of skeletal muscle gene expression [10].
• Removing myogenin before embryonic muscle development resulted in myofiber deficiencies identical to those observed in Myog-null mice [11].
• Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis [12].
• Cotransfection assays were performed with various combinations of Six and Eya to assess their effects on a potential natural target, myogenin promoter, and on a synthetic promoter, the thymidine kinase gene promoter fused to multimerized Six4 binding sites [13].
• It has been proposed that the myogenic factors, MyoD1 and myogenin, directly regulate MCK gene expression in the mouse by binding to its enhancer [14].

Anatomical context of Myog

• The pattern of expression of MyoD1 and myogenin during the early stages of muscle formation in the mouse embryo in vivo and in limb-bud explants cultured in vitro, indicates that they may have different functions in different types of muscle during development [12].
• In contrast, JunD, which shares DNA-binding specificity with JunB and c-Jun but is expressed constitutively in muscle cells, is an inefficient inhibitor of the trans-activating capacity of myogenin and MyoD [15].
• Myogenin, one of the MyoD family of proteins, is expressed early during somitogenesis and is required for myoblast fusion in vivo [16].
• In mice lacking myogenin, there is a severe deficiency of skeletal muscle, but some residual muscle fibers are present in mutant mice at birth [17].
• Their irregularly shaped somites expressed a somite marker gene Mox 1 but failed to express myogenin [18].

Associations of Myog with chemical compounds

• Notably, a complete absence of muscle regulatory markers such as MyoD and myogenin was observed in p65(tpr-met) highly expressing C2 clones [19].
• Myogenic cell lines were generated from unconverted C3H10T1/2 cells by 5-azacytidine treatment (Aza cell lines) and by stable transfection with MyoD1 (TD cell lines) or myogenin (TG cell lines) [20].
• In addition, these mice show elevated serum creatine kinase levels, consistent with the myo-necrosis observed morphologically [21].
• In doing so, it also activates expression of myogenin, MyoD, and endogenous herculin in NIH 3T3 recipients [22].
• Accelerated response of the myogenin gene to denervation in mutant mice lacking phosphorylation of myogenin at threonine 87 [23].

Physical interactions of Myog

• MyoD targets chromatin remodeling complexes to the myogenin locus prior to forming a stable DNA-bound complex [24].
• Furthermore, potential MyoD/myogenin-binding sequence motifs were identified in the 5' regulatory region of the Clc-1 gene [25].
• Myogenin binds to and represses c-fos promoter [26].
• In contrast with cells containing wild-type large T, those with the Rb binding site mutant large T showed the same up-regulation of myosine heavy chain and myogenin mRNA expression as control cells [27].
• These results support a model of transcriptional activation and stabilization of myogenin expression in which DNA-bound MEF2 recruits myogenic bHLH factors into an active but E1A-sensitive transcription factor complex [28].

Enzymatic interactions of Myog

• These disorders are correlated with low levels of expression of transcription factor myogenin and with the persistence of a large pool of hyperphosphorylated retinoblastoma protein [29].

Regulatory relationships of Myog

• BMP-2 completely inhibited the expression of myogenin mRNA by day 3 [30].
• These results demonstrate that MRF4 is able to substitute for myogenin to activate MRF4 expression and promote myofiber formation during the early stages of myogenesis [31].
• Finally, we show by in situ hybridization that the Id3 mRNA is co-expressed with the myogenic regulatory factor myogenin in somites and developing muscle during embryogenesis, although unlike the myogenic regulatory factors, Id3 is also expressed in many other locations in the embryo [32].
• We show that N-cadherin activation substitutes for the cell density in myogenic differentiation by promoting myogenin and troponin T expression [33].
• Myogenin-deficient fetuses that expressed the transgene also had more myosin, more and larger myofibers, and a more normal ribcage morphology than myogenin-deficient littermates without the transgene [31].

Co-localisations of Myog

• In mature myofibers, myogenin and Brg1 are preferentially co-localized to the myogenin promoter [34].

Other interactions of Myog

• Functional redundancy of the muscle-specific transcription factors Myf5 and myogenin [35].
• The number of MyoD- and Myogenin-expressing activated satellite cells after injury were significantly reduced in mutants [36].
• Antibodies directed specifically against Six1 or Six4 proteins reveal that each of these proteins is present in the embryo when myogenin is activated and constitutes a muscle-specific MEF3-binding activity in adult muscle nuclear extracts [16].
• Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis [37].
• In the mouse, myogenin, first detected at 8.5 days p.c., is expressed at the same time as BCK in myotomes [14].

Analytical, diagnostic and therapeutic context of Myog

• Loss of myogenin in postnatal life leads to normal skeletal muscle but reduced body size [11].
• Denervation of skeletal muscle reverses the effects of the nerve, and results in the reactivation of myogenin expression, as well as of other embryonic muscle proteins [38].
• Using in situ hybridization to analyze serial sections of E12.5 embryos, we found colocalization of CAT and endogenous myogenin transcripts in the primordial muscle of the head and limbs, in the intercostal muscle masses, and in the most caudal somites [38].
• Gene targeting studies have revealed hierarchical relationships between these and the other MRF genes, Mrf4 and myogenin, where the latter are regarded as differentiation genes [39].
• To understand the mechanism of activation, we performed chromatin immunoprecipitations analyzing the myogenin promoter [24].

References