To see the other types of publications on this topic, follow the link: My3D.
Journal articles on the topic 'My3D'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'My3D.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Patapoutian, A., J. K. Yoon, J. H. Miner, S. Wang, K. Stark, and B. Wold. "Disruption of the mouse MRF4 gene identifies multiple waves of myogenesis in the myotome." Development 121, no. 10 (October 1, 1995): 3347–58. http://dx.doi.org/10.1242/dev.121.10.3347.
Full textAbstract:
MRF4 (herculin/Myf-6) is one of the four member MyoD family of transcription factors identified by their ability to enforce skeletal muscle differentiation upon a wide variety of nonmuscle cell types. In this study the mouse germline MRF4 gene was disrupted by targeted recombination. Animals homozygous for the MRF4bh1 allele, a deletion of the functionally essential bHLH domain, displayed defective axial myogenesis and rib pattern formation, and they died at birth. Differences in somitogenesis between homozygous MRF4bh1 embryos and their wild-type littermates provided evidence for three distinct myogenic regulatory programs (My1-My3) in the somite, which correlate temporally and spatially with three waves of cellular recruitment to the expanding myotome. The first program (My1), marked initially by Myf-5 expression and followed by myogenin, began on schedule in the MRF4bh1/bh1 embryos at day 8 post coitum (E8). A second program (My2) was highly deficient in homozygous mutant MRF4 embryos, and normal expansion of the myotome failed. Moreover, expression of downstream muscle-specific genes, including FGF-6, which is a candidate regulator of inductive interactions, did not occur normally. The onset of MyoD expression around E10.5 in wild-type embryos marks a third myotomal program (My3), the execution of which was somewhat delayed in MRF4 mutant embryos but ultimately led to extensive myogenesis in the trunk. By E15 it appeared to have largely compensated for the defective My2 program in MRF4 mutants. Homozygous MRF4bh1 animals also showed improper rib pattern formation perhaps due to the absence of signals from cells expressing the My2 program. Finally, a later and relatively mild phenotype was detected in intercostal muscles of newborn animals.
2
Maleki, Soheila J., Catherine A. Royer, and Barry K. Hurlburt. "MyoD−E12 Heterodimers and MyoD−MyoD Homodimers Are Equally Stable†." Biochemistry 36, no. 22 (June 1997): 6762–67. http://dx.doi.org/10.1021/bi970262m.
Full text
3
Song, An, Qi Wang, Mark G. Goebl, and Maureen A. Harrington. "Phosphorylation of Nuclear MyoD Is Required for Its Rapid Degradation." Molecular and Cellular Biology 18, no. 9 (September 1, 1998): 4994–99. http://dx.doi.org/10.1128/mcb.18.9.4994.
Full textAbstract:
ABSTRACT MyoD is a basic helix-loop-helix transcription factor involved in the activation of genes encoding skeletal muscle-specific proteins. Independent of its ability to transactivate muscle-specific genes, MyoD can also act as a cell cycle inhibitor. MyoD activity is regulated by transcriptional and posttranscriptional mechanisms. While MyoD can be found phosphorylated, the functional significance of this posttranslation modification has not been established. MyoD contains several consensus cyclin-dependent kinase (CDK) phosphorylation sites. In these studies, we examined whether a link could be established between MyoD activity and phosphorylation at putative CDK sites. Site-directed mutagenesis of potential CDK phosphorylation sites in MyoD revealed that S200 is required for MyoD hyperphosphorylation as well as the normally short half-life of the MyoD protein. Additionally, we determined that turnover of the MyoD protein requires the proteasome and Cdc34 ubiquitin-conjugating enzyme activity. Results of these studies demonstrate that hyperphosphorylated MyoD is targeted for rapid degradation by the ubiquitin pathway. The targeted degradation of MyoD following CDK phosphorylation identifies a mechanism through which MyoD activity can be regulated coordinately with the cell cycle machinery (CDK2 and CDK4) and/or coordinately with the cellular transcriptional machinery (CDK7, CDK8, and CDK9).
4
Kitzmann, Magali, Marie Vandromme, Valerie Schaeffer, Gilles Carnac, Jean-Claude Labbé, Ned Lamb, and Anne Fernandez. "cdk1- and cdk2-Mediated Phosphorylation of MyoD Ser200 in Growing C2 Myoblasts: Role in Modulating MyoD Half-Life and Myogenic Activity." Molecular and Cellular Biology 19, no. 4 (April 1, 1999): 3167–76. http://dx.doi.org/10.1128/mcb.19.4.3167.
Full textAbstract:
ABSTRACT We have examined the role of protein phosphorylation in the modulation of the key muscle-specific transcription factor MyoD. We show that MyoD is highly phosphorylated in growing myoblasts and undergoes substantial dephosphorylation during differentiation. MyoD can be efficiently phosphorylated in vitro by either purified cdk1-cyclin B or cdk1 and cdk2 immunoprecipitated from proliferative myoblasts. Comparative two-dimensional tryptic phosphopeptide mapping combined with site-directed mutagenesis revealed that cdk1 and cdk2 phosphorylate MyoD on serine 200 in proliferative myoblasts. In addition, when the seven proline-directed sites in MyoD were individually mutated, only substitution of serine 200 to a nonphosphorylatable alanine (MyoD-Ala200) abolished the slower-migrating hyperphosphorylated form of MyoD, seen either in vitro after phosphorylation by cdk1-cyclin B or in vivo following overexpression in 10T1/2 cells. The MyoD-Ala200 mutant displayed activity threefold higher than that of wild-type MyoD in transactivation of an E-box-dependent reporter gene and promoted markedly enhanced myogenic conversion and fusion of 10T1/2 fibroblasts into muscle cells. In addition, the half-life of MyoD-Ala200 protein was longer than that of wild-type MyoD, substantiating a role of Ser200 phosphorylation in regulating MyoD turnover in proliferative myoblasts. Taken together, our data show that direct phosphorylation of MyoD Ser200 by cdk1 and cdk2 plays an integral role in compromising MyoD activity during myoblast proliferation.
5
Tintignac, Lionel A. J., Valentina Sirri, Marie Pierre Leibovitch, Yann Lécluse, Maria Castedo, Didier Metivier, Guido Kroemer, and Serge A. Leibovitch. "Mutant MyoD Lacking Cdc2 Phosphorylation Sites Delays M-Phase Entry." Molecular and Cellular Biology 24, no. 4 (February 15, 2004): 1809–21. http://dx.doi.org/10.1128/mcb.24.4.1809-1821.2004.
Full textAbstract:
ABSTRACT The transcription factors MyoD and Myf-5 control myoblast identity and differentiation. MyoD and Myf-5 manifest opposite cell cycle-specific expression patterns. Here, we provide evidence that MyoD plays a pivotal role at the G2/M transition by controlling the expression of p21Waf1/Cip1 (p21), which is believed to regulate cyclin B-Cdc2 kinase activity in G2. In growing myoblasts, MyoD reaccumulates during G2 concomitantly with p21 before entry into mitosis; MyoD is phosphorylated on Ser5 and Ser200 by cyclin B-Cdc2, resulting in a decrease of its stability and down-regulation of both MyoD and p21. Inducible expression of a nonphosphorylable MyoD A5/A200 enhances the MyoD interaction with the coactivator P/CAF, thereby stimulating the transcriptional activation of a luciferase reporter gene placed under the control of the p21 promoter. MyoD A5/A200 causes sustained p21 expression, which inhibits cyclin B-Cdc2 kinase activity in G2 and delays M-phase entry. This G2 arrest is not observed in p21−/− cells. These results show that in cycling cells MyoD functions as a transcriptional activator of p21 and that MyoD phosphorylation is required for G2/M transition.
6
Montarras, D., F. Aurade, T. Johnson, J. IIan, F. Gros, and C. Pinset. "Autonomous differentiation in the mouse myogenic cell line, C2, involves a mutual positive control between insulin-like growth factor II and MyoD, operating as early as at the myoblast stage." Journal of Cell Science 109, no. 3 (March 1, 1996): 551–60. http://dx.doi.org/10.1242/jcs.109.3.551.
Full textAbstract:
We have studied the contribution of the endogenous production of insulin-like growth factor II (IGFII) and of the muscle regulatory factor, MyoD, to the autonomy of differentiation in isolated skeletal myoblasts. Inhibition of MyoD and IGFII gene expression in myoblasts of the mouse myogenic cell line, C2, was achieved by transfection and selection of stably transfected cells (anti-MyoD and anti-IGFII cells) with vectors producing MyoD or IGFII antisense RNA. We observed that inhibiting either MyoD or IGFII has multiple and similar consequences. In addition to the inhibition of the target gene, expression of MyoD transcripts in anti-IGFII myoblasts and expression of IGFII in anti-MyoD myoblasts were also abolished, whereas accumulation of transcripts for the muscle regulatory factor, Myf5, was markedly increased in both cell types. However, despite this Myf5 up-regulation, both anti-IGFII and anti-MyoD myoblasts lost the ability to undergo autonomous differentiation (differentiation in the absence of added IGF), further indicating that Myf5 and MyoD are not strictly interchangeable. Additional evidence of a link between MyoD and IGFII was obtained: (1) forced expression of the MyoD cDNA stimulated IGFII gene expression, and (2) treatment of C2 myoblasts with fibroblast growth factor, not only diminished MyoD expression and compromised differentiation as previously shown by others, but also abolished IGFII expression. These experiments showing loss or gain of function argue in favor of a mutual positive control between IGFII and MyoD operating as early as the myoblast stage.
7
Thorburn, A. M., P. A. Walton, and J. R. Feramisco. "MyoD induced cell cycle arrest is associated with increased nuclear affinity of the Rb protein." Molecular Biology of the Cell 4, no. 7 (July 1993): 705–13. http://dx.doi.org/10.1091/mbc.4.7.705.
Full textAbstract:
In studying the mechanism through which the myogenic determination protein MyoD prevents entry into the S phase of the cell cycle, we have found a relationship between MyoD and the retinoblastoma (Rb) tumor suppressor protein. By direct needle microinjection of purified recombinant MyoD protein into quiescent fibroblasts, which were then induced to proliferate by serum, we found that MyoD arrested progression of the cell cycle, in agreement with studies utilizing expression constructs for MyoD. By studying temporal changes in cells injected with MyoD protein, it was found that MyoD did not prevent serum induced expression of the protooncogene c-Fos, an event that occurs in the G0 to G1 transition of the cycle. Injection of the MyoD protein as late as 8 h after the addition of serum still caused an inhibition in DNA synthesis, suggesting that MyoD inhibits the G1 to S transition as opposed to the G0 to G1 transition. MyoD injection did not prevent the expression of cyclin A. However MyoD injection did result in a block in the increase in Rb extractibility normally seen in late G1 phase cells. As this phenomenon is associated with the hyperphosphorylation of Rb at this point in the cell cycle and is correlated with progression into S phase, this provides further evidence that MyoD blocks the cycle late in G1.
8
Staib, Jessica L., Steven J. Swoap, and Scott K. Powers. "Diaphragm contractile dysfunction in MyoD gene-inactivated mice." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 283, no. 3 (September 1, 2002): R583—R590. http://dx.doi.org/10.1152/ajpregu.00080.2002.
Full textAbstract:
MyoD is one of four myogenic regulatory factors found exclusively in skeletal muscle. In an effort to better understand the role that MyoD plays in determining muscle contractile properties, we examined the effects of MyoD deletion on both diaphragmatic contractile properties and myosin heavy chain (MHC) phenotype. Regions of the costal diaphragm from wild-type and MyoD knockout [ MyoD (−/−)] adult male BALB/c mice ( n = 8/group) were removed, and in vitro diaphragmatic contractile properties were measured. Diaphragmatic contractile measurements revealed that MyoD (−/−) animals exhibited a significant ( P < 0.05) downward shift in the force-frequency relationship, a decrement in maximal specific tension (Po; −33%), a decline in maximal shortening velocity (Vmax; −37%), and concomitant decrease in peak power output (−47%). Determination of MHC isoforms in the diaphragm via gel electrophoresis revealed that MyoD elimination resulted in a fast-to-slow shift ( P < 0.05) in the MHC phenotype toward MHC types IIA and IIX in MyoD (−/−) animals. These data indicate that MyoD deletion results in a decrease in diaphragmatic submaximal force generation and Po, along with decrements in both Vmax and peak power output. Hence, MyoD plays an important role in determining diaphragmatic contractile properties.
9
Reynaud, Emmanuel G., Karine Pelpel, Martine Guillier, Marie Pierre Leibovitch, and Serge A. Leibovitch. "p57Kip2 Stabilizes the MyoD Protein by Inhibiting Cyclin E-Cdk2 Kinase Activity in Growing Myoblasts." Molecular and Cellular Biology 19, no. 11 (November 1, 1999): 7621–29. http://dx.doi.org/10.1128/mcb.19.11.7621.
Full textAbstract:
ABSTRACT We show that expression of p57Kip2, a potent tight-binding inhibitor of several G1cyclin–cyclin-dependent kinase (Cdk) complexes, increases markedly during C2C12 myoblast differentiation. We examined the effect of p57Kip2 on the activity of the transcription factor MyoD. In transient transfection assays, transcriptional transactivation of the mouse muscle creatine kinase promoter by MyoD was enhanced by the Cdk inhibitors. In addition, p57Kip2, p21Cip1, and p27Kip1 but not p16Ink4a induced an increased level of MyoD protein, and we show that MyoD, an unstable nuclear protein, was stabilized by p57Kip2. Forced expression of p57Kip2 correlated with hypophosphorylation of MyoD in C2C12 myoblasts. A dominant-negative Cdk2 mutant arrested cells at the G1 phase transition and induced hypophosphorylation of MyoD. Furthermore, phosphorylation of MyoD by purified cyclin E-Cdk2 complexes was inhibited by p57Kip2. In addition, the NH2 domain of p57Kip2 necessary for inhibition of cyclin E-Cdk2 activity was sufficient to inhibit MyoD phosphorylation and to stabilize it, leading to its accumulation in proliferative myoblasts. Taken together, our data suggest that repression of cyclin E-Cdk2-mediated phosphorylation of MyoD by p57Kip2 could play an important role in the accumulation of MyoD at the onset of myoblast differentiation.
10
Goldhamer, D. J., B. P. Brunk, A. Faerman, A. King, M. Shani, and C. P. Emerson. "Embryonic activation of the myoD gene is regulated by a highly conserved distal control element." Development 121, no. 3 (March 1, 1995): 637–49. http://dx.doi.org/10.1242/dev.121.3.637.
Full textAbstract:
MyoD belongs to a small family of basic helix-loop-helix transcription factors implicated in skeletal muscle lineage determination and differentiation. Previously, we identified a transcriptional enhancer that regulates the embryonic expression of the human myoD gene. This enhancer had been localized to a 4 kb fragment located 18 to 22 kb upstream of the myoD transcriptional start site. We now present a molecular characterization of this enhancer. Transgenic and transfection analyses localize the myoD enhancer to a core sequence of 258 bp. In transgenic mice, this enhancer directs expression of a lacZ reporter gene to skeletal muscle compartments in a spatiotemporal pattern indistinguishable from the normal myoD expression domain, and distinct from expression patterns reported for the other myogenic factors. In contrast to the myoD promoter, the myoD enhancer shows striking conservation between humans and mice both in its sequence and its distal position. Furthermore, a myoD enhancer/heterologous promoter construct exhibits muscle-specific expression in transgenic mice, demonstrating that the myoD promoter is dispensable for myoD activation. With the exception of E-boxes, the myoD enhancer has no apparent sequence similarity with regulatory regions of other characterized muscle-specific structural or regulatory genes. Mutation of these E-boxes, however, does not affect the pattern of lacZ transgene expression, suggesting that myoD activation in the embryo is E-box-independent. DNase I protection assays reveal multiple nuclear protein binding sites in the core enhancer, although none are strictly muscle-specific. Interestingly, extracts from myoblasts and 10T1/2 fibroblasts yield identical protection profiles, indicating a similar complement of enhancer-binding factors in muscle and this non-muscle cell type. However, a clear difference exists between myoblasts and 10T1/2 cells (and other non-muscle cell types) in the chromatin structure of the chromosomal myoD core enhancer, suggesting that the myoD enhancer is repressed by epigenetic mechanisms in 10T1/2 cells. These data indicate that myoD activation is regulated at multiple levels by mechanisms that are distinct from those controlling other characterized muscle-specific genes.
11
Harvey, R. P. "The Xenopus MyoD gene: an unlocalised maternal mRNA predates lineage-restricted expression in the early embryo." Development 108, no. 4 (April 1, 1990): 669–80. http://dx.doi.org/10.1242/dev.108.4.669.
Full textAbstract:
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.
12
Vandromme, M., G. Carnac, C. Gauthier-Rouviere, D. Fesquet, N. Lamb, and A. Fernandez. "Nuclear import of the myogenic factor MyoD requires cAMP-dependent protein kinase activity but not the direct phosphorylation of MyoD." Journal of Cell Science 107, no. 2 (February 1, 1994): 613–20. http://dx.doi.org/10.1242/jcs.107.2.613.
Full textAbstract:
MyoD is a nuclear phosphoprotein that belongs to the family of myogenic regulatory factors and acts in the transcriptional activation of muscle-specific genes. We have investigated the role of cAMP-dependent protein kinase (A-kinase) in modulating the nuclear locale of MyoD. Purified MyoD protein microinjected into the cytoplasm of rat embryo fibroblasts is rapidly translocated into the nucleus. Inhibition of A-kinase activity through injection of the specific inhibitory peptide PKI prevents this nuclear localisation. This inhibition of nuclear location is specifically reversed by injection of purified A-kinase catalytic subunit, showing the requirement for A-kinase in the nuclear import of MyoD. Site-directed mutagenesis of all the putative sites for A-kinase-dependent phosphorylation on MyoD, substituting serine or threonine residues for the non-phosphorylatable amino acid alanine, had no effect on nuclear import of mutated MyoD. These data exclude the possibility that the effect of A-kinase on the nuclear translocation of MyoD is mediated by direct phosphorylation of MyoD and imply that A-kinase operates through phosphorylation of components involved in the nuclear transport of MyoD.
13
L'honore, Aurore, Ned J. Lamb, Marie Vandromme, Patric Turowski, Gilles Carnac, and Anne Fernandez. "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 14, no. 5 (May 2003): 2151–62. http://dx.doi.org/10.1091/mbc.e02-07-0451.
Full textAbstract:
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.
14
Seward, David J., John C. Haney, Michael A. Rudnicki, and Steven J. Swoap. "bHLH transcription factor MyoD affects myosin heavy chain expression pattern in a muscle-specific fashion." American Journal of Physiology-Cell Physiology 280, no. 2 (February 1, 2001): C408—C413. http://dx.doi.org/10.1152/ajpcell.2001.280.2.c408.
Full textAbstract:
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.
15
Olson, Eric N., and William H. Klein. "Muscle Minus MyoD." Developmental Biology 202, no. 2 (October 1998): 153–56. http://dx.doi.org/10.1006/dbio.1998.9020.
Full text
16
Sabourin, Luc A., Adele Girgis-Gabardo, Patrick Seale, Atsushi Asakura, and Michael A. Rudnicki. "Reduced Differentiation Potential of Primary MyoD−/− Myogenic Cells Derived from Adult Skeletal Muscle." Journal of Cell Biology 144, no. 4 (February 22, 1999): 631–43. http://dx.doi.org/10.1083/jcb.144.4.631.
Full textAbstract:
To gain insight into the regeneration deficit of MyoD−/− muscle, we investigated the growth and differentiation of cultured MyoD−/− myogenic cells. Primary MyoD−/− myogenic cells exhibited a stellate morphology distinct from the compact morphology of wild-type myoblasts, and expressed c-met, a receptor tyrosine kinase expressed in satellite cells. However, MyoD−/− myogenic cells did not express desmin, an intermediate filament protein typically expressed in cultured myoblasts in vitro and myogenic precursor cells in vivo. Northern analysis indicated that proliferating MyoD−/− myogenic cells expressed fourfold higher levels of Myf-5 and sixfold higher levels of PEA3, an ETS-domain transcription factor expressed in newly activated satellite cells. Under conditions that normally induce differentiation, MyoD−/− cells continued to proliferate and with delayed kinetics yielded reduced numbers of predominantly mononuclear myocytes. Northern analysis revealed delayed induction of myogenin, MRF4, and other differentiation-specific markers although p21 was upregulated normally. Expression of M-cadherin mRNA was severely decreased whereas expression of IGF-1 was markedly increased in MyoD−/− myogenic cells. Mixing of lacZ-labeled MyoD−/− cells and wild-type myoblasts revealed a strict autonomy in differentiation potential. Transfection of a MyoD-expression cassette restored cytomorphology and rescued the differentiation deficit. We interpret these data to suggest that MyoD−/− myogenic cells represent an intermediate stage between a quiescent satellite cell and a myogenic precursor cell.
17
Scionti, Isabella, Shinichiro Hayashi, Sandrine Mouradian, Emmanuelle Girard, Joana Esteves de Lima, Véronique Morel, Thomas Simonet, et al. "LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription." Cell Reports 18, no. 8 (February 2017): 1996–2006. http://dx.doi.org/10.1016/j.celrep.2017.01.078.
Full text
18
Johnston, L. A., S. J. Tapscott, and H. Eisen. "Sodium butyrate inhibits myogenesis by interfering with the transcriptional activation function of MyoD and myogenin." Molecular and Cellular Biology 12, no. 11 (November 1992): 5123–30. http://dx.doi.org/10.1128/mcb.12.11.5123.
Full textAbstract:
Sodium butyrate reversibly inhibits muscle differentiation and blocks the expression of many muscle-specific genes in both proliferating myoblasts and differentiated myotubes. We investigated the role of the basic helix-loop-helix (bHLH) myogenic determinator proteins MyoD and myogenin in this inhibition. Our data suggest that both MyoD and myogenin are not able to function as transcriptional activators in the presence of butyrate, although both apparently retain the ability to bind DNA. Transcription of MyoD itself is extinguished in butyrate-treated myoblasts and myotubes, an effect that may be due to the inability of MyoD to autoactivate its own transcription. We present evidence that the HLH region of MyoD is essential for butyrate inhibition of MyoD. In contrast to MyoD and myogenin, butyrate does not inhibit the ubiquitous basic HLH protein E2-5 from functioning as a transcriptional activator.
19
Johnston, L. A., S. J. Tapscott, and H. Eisen. "Sodium butyrate inhibits myogenesis by interfering with the transcriptional activation function of MyoD and myogenin." Molecular and Cellular Biology 12, no. 11 (November 1992): 5123–30. http://dx.doi.org/10.1128/mcb.12.11.5123-5130.1992.
Full textAbstract:
Sodium butyrate reversibly inhibits muscle differentiation and blocks the expression of many muscle-specific genes in both proliferating myoblasts and differentiated myotubes. We investigated the role of the basic helix-loop-helix (bHLH) myogenic determinator proteins MyoD and myogenin in this inhibition. Our data suggest that both MyoD and myogenin are not able to function as transcriptional activators in the presence of butyrate, although both apparently retain the ability to bind DNA. Transcription of MyoD itself is extinguished in butyrate-treated myoblasts and myotubes, an effect that may be due to the inability of MyoD to autoactivate its own transcription. We present evidence that the HLH region of MyoD is essential for butyrate inhibition of MyoD. In contrast to MyoD and myogenin, butyrate does not inhibit the ubiquitous basic HLH protein E2-5 from functioning as a transcriptional activator.
20
Kudou, Kensuke, Tetsuro Komatsu, Jumpei Nogami, Kazumitsu Maehara, Akihito Harada, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara, and Yasuyuki Ohkawa. "The requirement of Mettl3-promoted MyoD mRNA maintenance in proliferative myoblasts for skeletal muscle differentiation." Open Biology 7, no. 9 (September 2017): 170119. http://dx.doi.org/10.1098/rsob.170119.
Full textAbstract:
Myogenic progenitor/stem cells retain their skeletal muscle differentiation potential by maintaining myogenic transcription factors such as MyoD. However, the mechanism of how MyoD expression is maintained in proliferative progenitor cells has not been elucidated. Here, we found that MyoD expression was reduced at the mRNA level by cell cycle arrest in S and G2 phases, which in turn led to the absence of skeletal muscle differentiation. The reduction of MyoD mRNA was correlated with the reduced expression of factors regulating RNA metabolism, including methyltransferase like 3 (Mettl3), which induces N 6 -methyladenosine (m 6 A) modifications of RNA. Knockdown of Mettl3 revealed that MyoD RNA was specifically downregulated and that this was caused by a decrease in processed, but not unprocessed, mRNA. Potential m 6 A modification sites were profiled by m 6 A sequencing and identified within the 5′ untranslated region (UTR) of MyoD mRNA. Deletion of the 5′ UTR revealed that it has a role in MyoD mRNA processing. These data showed that Mettl3 is required for MyoD mRNA expression in proliferative myoblasts.
21
Wyzykowski, Jeffrey C., Therry I. Winata, Natalia Mitin, Elizabeth J. Taparowsky, and Stephen F. Konieczny. "Identification of Novel MyoD Gene Targets in Proliferating Myogenic Stem Cells." Molecular and Cellular Biology 22, no. 17 (September 1, 2002): 6199–208. http://dx.doi.org/10.1128/mcb.22.17.6199-6208.2002.
Full textAbstract:
ABSTRACT A major control point for skeletal myogenesis revolves around the muscle basic helix-loop-helix gene family that includes MyoD, Myf-5, myogenin, and MRF4. Myogenin and MRF4 are thought to be essential to terminal differentiation events, whereas MyoD and Myf-5 are critical to establishing the myogenic cell lineage and producing committed, undifferentiated myogenic stem cells (myoblasts). Although mouse genetic studies have revealed the importance of MyoD and Myf-5 for myoblast development, the genetic targets of MyoD and Myf-5 activity in undifferentiated myoblasts remain unknown. In this study, we investigated the function of MyoD as a transcriptional activator in undifferentiated myoblasts. By using conditional expression of MyoD, in conjunction with suppression subtractive hybridizations, we show that the Id3 and NP1 (neuronal pentraxin 1) genes become transcriptionally active following MyoD induction in undifferentiated myoblasts. Activation of Id3 and NP1 represents a stable, heritable event that does not rely on continued MyoD activity and is not subject to negative regulation by an activated H-Ras G12V protein. These results are the first to demonstrate that MyoD functions as a transcriptional activator in myogenic stem cells and that this key myogenic regulatory factor exhibits different gene target specificities, depending upon the cellular environment.
22
Kitzmann, Magali, Gilles Carnac, Marie Vandromme, Michael Primig, Ned J. C. Lamb, and Anne Fernandez. "The Muscle Regulatory Factors MyoD and Myf-5 Undergo Distinct Cell Cycle–specific Expression in Muscle Cells." Journal of Cell Biology 142, no. 6 (September 21, 1998): 1447–59. http://dx.doi.org/10.1083/jcb.142.6.1447.
Full textAbstract:
The muscle regulators MyoD and Myf-5 control cell cycle withdrawal and induction of differentiation in skeletal muscle cells. By immunofluorescence analysis, we show that MyoD and Myf-5 expression patterns become mutually exclusive when C2 cells are induced to differentiate with Myf-5 staining present in cells which fail to differentiate. Isolation of these undifferentiated cells reveals that upon serum stimulation they reenter the cell cycle, express MyoD and downregulate Myf-5. Similar regulations of MyoD and Myf-5 were observed using cultured primary myoblasts derived from satellite cells. To further analyze these regulations of MyoD and Myf-5 expression, we synchronized proliferating myoblasts. Analysis of MyoD and Myf-5 expression during cell cycle progression revealed distinct and contrasting profiles of expression. MyoD is absent in G0, peaks in mid-G1, falls to its minimum level at G1/S and reaugments from S to M. In contrast, Myf-5 protein is high in G0, decreases during G1 and reappears at the end of G1 to remain stable until mitosis. These data demonstrate that the two myogenic factors MyoD and Myf-5 undergo specific and distinct cell cycle–dependent regulation, thus establishing a correlation between the cell cycle–specific ratios of MyoD and Myf-5 and the capacity of cells to differentiate: (a) in G1, when cells express high levels of MyoD and enter differentiation; (b) in G0, when cells express high levels of Myf-5 and fail to differentiate.
23
Lenormand, J. L., B. Benayoun, M. Guillier, M. Vandromme, M. P. Leibovitch, and S. A. Leibovitch. "Mos activates myogenic differentiation by promoting heterodimerization of MyoD and E12 proteins." Molecular and Cellular Biology 17, no. 2 (February 1997): 584–93. http://dx.doi.org/10.1128/mcb.17.2.584.
Full textAbstract:
The activities of myogenic basic helix-loop-helix (bHLH) factors are regulated by a number of different positive and negative signals. Extensive information has been published about the molecular mechanisms that interfere with the process of myogenic differentiation, but little is known about the positive signals. We previously showed that overexpression of rat Mos in C2C12 myoblasts increased the expression of myogenic markers whereas repression of Mos products by antisense RNAs inhibited myogenic differentiation. In the present work, our results show that the rat mos proto-oncogene activates transcriptional activity of MyoD protein. In transient transfection assays, Mos promotes transcriptional transactivation by MyoD of the muscle creatine kinase enhancer and/or a reporter gene linked to MyoD-DNA binding sites. Physical interaction between Mos and MyoD, but not with E12, is demonstrated in vivo by using the two-hybrid approach with C3H10T1/2 cells and in vitro by using the glutathione S-transferase (GST) pull-down assays. Unphosphorylated MyoD from myogenic cell lysates and/or bacterially expressed MyoD physically interacts with Mos. This interaction occurs via the helix 2 region of MyoD and a highly conserved region in Mos proteins with 40% similarity to the helix 2 domain of the E-protein class of bHLH factors. Phosphorylation of MyoD by activated GST-Mos protein inhibits the DNA-binding activity of MyoD homodimers and promotes MyoD-E12 heterodimer formation. These data support a novel function for Mos as a mediator (coregulator) of muscle-specific gene(s) expression.
24
Ishibashi, Jeff, Robert L. Perry, Atsushi Asakura, and Michael A. Rudnicki. "MyoD induces myogenic differentiation through cooperation of its NH2- and COOH-terminal regions." Journal of Cell Biology 171, no. 3 (November 7, 2005): 471–82. http://dx.doi.org/10.1083/jcb.200502101.
Full textAbstract:
MyoD and Myf5 are basic helix-loop-helix transcription factors that play key but redundant roles in specifying myogenic progenitors during embryogenesis. However, there are functional differences between the two transcription factors that impact myoblast proliferation and differentiation. Target gene activation could be one such difference. We have used microarray and polymerase chain reaction approaches to measure the induction of muscle gene expression by MyoD and Myf5 in an in vitro model. In proliferating cells, MyoD and Myf5 function very similarly to activate the expression of likely growth phase target genes such as L-myc, m-cadherin, Mcpt8, Runx1, Spp1, Six1, IGFBP5, and Chrnβ1. MyoD, however, is strikingly more effective than Myf5 at inducing differentiation-phase target genes. This distinction between MyoD and Myf5 results from a novel and unanticipated cooperation between the MyoD NH2- and COOH-terminal regions. Together, these results support the notion that Myf5 functions toward myoblast proliferation, whereas MyoD prepares myoblasts for efficient differentiation.
25
Zhang, Keman, Jingfeng Sha, and Marian L. Harter. "Activation of Cdc6 by MyoD is associated with the expansion of quiescent myogenic satellite cells." Journal of Cell Biology 188, no. 1 (January 4, 2010): 39–48. http://dx.doi.org/10.1083/jcb.200904144.
Full textAbstract:
MyoD is a transcriptional factor that is required for the differentiation of muscle stem cells (satellite cells). In this study, we describe a previously unknown function for MyoD in regulating a gene (Cdc6) that is vital to endowing chromatin with the capability of replicating DNA. In C2C12 and primary mouse myoblasts, we show that MyoD can occupy an E-box within the promoter of Cdc6 and that this association, along with E2F3a, is required for its activity. MyoD and Cdc6 are both expressed after quiescent C2C12 myoblasts or satellite cells in association with myofibers are stimulated for growth, but MyoD appears at least 2–3 h earlier than Cdc6. Finally, knockdown of MyoD impairs the ability of C2C12 cells to express Cdc6 after leaving quiescence, and as a result, they cannot fully progress into S phase. Our results define a mechanism by which MyoD helps myogenic satellite cells to enter into the first round of DNA replication after transitioning out of quiescence.
26
Park, Sooyeon, Ji-Min Park, Chul-Hyung Kang, and Jung-Hoon Yoon. "Aestuariivivens insulae gen. nov., sp. nov., isolated from a tidal flat." International Journal of Systematic and Evolutionary Microbiology 65, Pt_6 (June 1, 2015): 1883–88. http://dx.doi.org/10.1099/ijs.0.000192.
Full textAbstract:
A Gram-stain-negative, non-motile, aerobic, ovoid or rod-shaped bacterium, designated AH-MY3T, was isolated from a tidal flat on Aphae island of the south-western sea, South Korea, and subjected to a polyphasic taxonomic study. Strain AH-MY3T grew optimally at 35 °C, at pH 7.0–8.0 and in the presence of 2.0–3.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain AH-MY3T joined the cluster comprising the type strains of Yeosuana aromativorans, Snuella lapsa and Meridianimaribacter flavus, showing sequence similarities of 93.9, 93.7 and 92.6 %, respectively. Strain AH-MY3T exhibited 16S rRNA gene sequence similarity values of 94.0–94.7 % to the type strains of ‘Aestuariibaculum scopimerae’, Winogradskyella aquimaris, Winogradskyella poriferorum and Gaetbulibacter aestuarii. Strain AH-MY3T contained MK-6 as the predominant menaquinone. The fatty acid and polar lipid profiles of strain AH-MY3T could be distinguished from those of the type strains of phylogenetically related taxa. The DNA G+C content of strain AH-MY3T was 37 mol%. The phylogenetic data and differential chemotaxonomic and other phenotypic properties revealed that strain AH-MY3T represents a novel genus and species within the family Flavobacteriaceae, for which the name Aestuariivivens insulae gen. nov., sp. nov. is proposed. The type strain of Aestuariivivens insulae is AH-MY3T ( = KCTC 42350T = NBRC 110723T).
27
Ishido, Minenori, Katsuya Kami, and Mitsuhiko Masuhara. "In vivo expression patterns of MyoD, p21, and Rb proteins in myonuclei and satellite cells of denervated rat skeletal muscle." American Journal of Physiology-Cell Physiology 287, no. 2 (August 2004): C484—C493. http://dx.doi.org/10.1152/ajpcell.00080.2004.
Full textAbstract:
MyoD, a myogenic regulatory factor, is rapidly expressed in adult skeletal muscles in response to denervation. However, the function(s) of MyoD expressed in denervated muscle has not been adequately elucidated. In vitro, it directly transactivates cyclin-dependent kinase inhibitor p21 (p21) and retinoblastoma protein (Rb), a downstream target of p21. These factors then act to regulate cell cycle withdrawal and antiapoptotic cell death. Using immunohistochemical approaches, we characterized cell types expressing MyoD, p21, and Rb and the relationship among these factors in the myonucleus of denervated muscles. In addition, we quantitatively examined the time course changes and expression patterns among distinct myofiber types of MyoD, p21, and Rb during denervation. Denervation induced MyoD expression in myonuclei and satellite cell nuclei, whereas p21 and Rb were found only in myonuclei. Furthermore, coexpression of MyoD, p21, and Rb was induced in the myonucleus, and quantitative analysis of these factors determined that there was no difference among the three myofiber types. These observations suggest that MyoD may function in myonuclei in response to denervation to protect against denervation-induced apoptosis via perhaps the activation of p21 and Rb, and function of MyoD expressed in satellite cell nuclei may be negatively regulated. The present study provides a molecular basis to further understand the function of MyoD expressed in the myonuclei and satellite cell nuclei of denervated skeletal muscle.
28
Miner, J. H., and B. J. Wold. "c-myc inhibition of MyoD and myogenin-initiated myogenic differentiation." Molecular and Cellular Biology 11, no. 5 (May 1991): 2842–51. http://dx.doi.org/10.1128/mcb.11.5.2842.
Full textAbstract:
In vertebrate development, a prominent feature of several cell lineages is the coupling of cell cycle regulation with terminal differentiation. We have investigated the basis of this relationship in the skeletal muscle lineage by studying the effects of the proliferation-associated regulator, c-myc, on the differentiation of MyoD-initiated myoblasts. Transient cotransfection assays in NIH 3T3 cells using MyoD and c-myc expression vectors demonstrated c-myc suppression of MyoD-initiated differentiation. A stable cell system was also developed in which MyoD expression was constitutive, while myc levels could be elevated conditionally. Induction of this conditional c-myc suppressed myogenesis effectively, even in the presence of MyoD. c-myc suppression also prevented up-regulation of a relative of MyoD, myogenin, which is normally expressed at the onset of differentiation in all muscle cell lines examined and may be essential for differentiation. Additional experiments tested whether failure to differentiate in the presence of myc could be overcome by providing myogenin ectopically. Cotransfection of c-myc with myogenin, MyoD, or a mixture of myogenin and MyoD showed that neither myogenin alone nor myogenin plus MyoD together could bypass the c-myc block. The effects of c-myc were further dissected by showing that c-myc can inhibit differentiation independently of Id, a negative regulator of muscle differentiation. These results lead us to propose that c-myc and Id constitute independent negative regulators of muscle differentiation, while myogenin and any of the other three related myogenic factors (MyoD, Myf-5, and MRF4/herculin/Myf-6) act as positive regulators.
29
Miner, J. H., and B. J. Wold. "c-myc inhibition of MyoD and myogenin-initiated myogenic differentiation." Molecular and Cellular Biology 11, no. 5 (May 1991): 2842–51. http://dx.doi.org/10.1128/mcb.11.5.2842-2851.1991.
Full textAbstract:
In vertebrate development, a prominent feature of several cell lineages is the coupling of cell cycle regulation with terminal differentiation. We have investigated the basis of this relationship in the skeletal muscle lineage by studying the effects of the proliferation-associated regulator, c-myc, on the differentiation of MyoD-initiated myoblasts. Transient cotransfection assays in NIH 3T3 cells using MyoD and c-myc expression vectors demonstrated c-myc suppression of MyoD-initiated differentiation. A stable cell system was also developed in which MyoD expression was constitutive, while myc levels could be elevated conditionally. Induction of this conditional c-myc suppressed myogenesis effectively, even in the presence of MyoD. c-myc suppression also prevented up-regulation of a relative of MyoD, myogenin, which is normally expressed at the onset of differentiation in all muscle cell lines examined and may be essential for differentiation. Additional experiments tested whether failure to differentiate in the presence of myc could be overcome by providing myogenin ectopically. Cotransfection of c-myc with myogenin, MyoD, or a mixture of myogenin and MyoD showed that neither myogenin alone nor myogenin plus MyoD together could bypass the c-myc block. The effects of c-myc were further dissected by showing that c-myc can inhibit differentiation independently of Id, a negative regulator of muscle differentiation. These results lead us to propose that c-myc and Id constitute independent negative regulators of muscle differentiation, while myogenin and any of the other three related myogenic factors (MyoD, Myf-5, and MRF4/herculin/Myf-6) act as positive regulators.
30
Hirai, Hiroyuki, Mayank Verma, Shuichi Watanabe, Christopher Tastad, Yoko Asakura, and Atsushi Asakura. "MyoD regulates apoptosis of myoblasts through microRNA-mediated down-regulation of Pax3." Journal of Cell Biology 191, no. 2 (October 18, 2010): 347–65. http://dx.doi.org/10.1083/jcb.201006025.
Full textAbstract:
The molecules that regulate the apoptosis cascade are also involved in differentiation and syncytial fusion in skeletal muscle. MyoD is a myogenic transcription factor that plays essential roles in muscle differentiation. We noticed that MyoD−/− myoblasts display remarkable resistance to apoptosis by down-regulation of miR-1 (microRNA-1) and miR-206 and by up-regulation of Pax3. This resulted in transcriptional activation of antiapoptotic factors Bcl-2 and Bcl-xL. Forced MyoD expression induces up-regulation of miR-1 and miR-206 and down-regulation of Pax3, Bcl-2, and Bcl-xL along with increased apoptosis in MyoD−/− myoblasts. In contrast, MyoD gene knockdown increases cell survival of wild-type myoblasts. The 3′ untranslated region of Pax3 mRNA contains two conserved miR-1/miR-206–binding sites, which are required for targeting of these microRNAs (miRNAs). Therefore, these data suggest that MyoD not only regulates terminal differentiation but also apoptosis through miRNA-mediated down-regulation of Pax3. Finally, MyoD, miR-1, and miR-206 are all down-regulated in quiescent satellite cells, which may be required for maintenance of muscle stem cells.
31
Kim, Chang-Hoon, Hannah Neiswender, Eun Joo Baik, Wen C. Xiong, and Lin Mei. "β-Catenin Interacts with MyoD and Regulates Its Transcription Activity." Molecular and Cellular Biology 28, no. 9 (March 3, 2008): 2941–51. http://dx.doi.org/10.1128/mcb.01682-07.
Full textAbstract:
ABSTRACT Wnt regulation of muscle development is thought to be mediated by the β-catenin-TCF/LEF-dependent canonical pathway. Here we demonstrate that β-catenin, not TCF/LEF, is required for muscle differentiation. We showed that β-catenin interacts directly with MyoD, a basic helix-loop-helix transcription factor essential for muscle differentiation and enhances its binding to E box elements and transcriptional activity. MyoD-mediated transactivation is inhibited in muscle cells when β-catenin is deficient or the interaction between MyoD and β-catenin is disrupted. These results demonstrate that β-catenin is necessary for MyoD function, identifying MyoD as an effector in the Wnt canonical pathway.
32
Jung, Eun-Shil, Ye-Ji Sim, Hoe-Su Jeong, Su-Jin Kim, Ye-Jin Yun, Joo-Hoon Song, Su-Hee Jeon, et al. "Jmjd2C increases MyoD transcriptional activity through inhibiting G9a-dependent MyoD degradation." Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 1849, no. 8 (August 2015): 1081–94. http://dx.doi.org/10.1016/j.bbagrm.2015.07.001.
Full text
33
Hamamori, Y., H. Y. Wu, V. Sartorelli, and L. Kedes. "The basic domain of myogenic basic helix-loop-helix (bHLH) proteins is the novel target for direct inhibition by another bHLH protein, Twist." Molecular and Cellular Biology 17, no. 11 (November 1997): 6563–73. http://dx.doi.org/10.1128/mcb.17.11.6563.
Full textAbstract:
In vertebrates, the basic helix-loop-helix (bHLH) protein Twist may be involved in the negative regulation of cellular determination and in the differentiation of several lineages, including myogenesis, osteogenesis, and neurogenesis. Although it has been shown that mouse twist (M-Twist) (i) sequesters E proteins, thus preventing formation of myogenic E protein-MyoD complexes and (ii) inhibits the MEF2 transcription factor, a cofactor of myogenic bHLH proteins, overexpression of E proteins and MEF2 failed to rescue the inhibitory effects of M-Twist on MyoD. We report here that M-Twist physically interacts with the myogenic bHLH proteins in vitro and in vivo and that this interaction is required for the inhibition of MyoD by M-Twist. In contrast to the conventional HLH-HLH domain interaction formed in the MyoD/E12 heterodimer, this novel type of interaction uses the basic domains of the two proteins. While the MyoD HLH domain without the basic domain failed to interact with M-Twist, a MyoD peptide containing only the basic and helix 1 regions was sufficient to interact with M-Twist, suggesting that the basic domain contacts M-Twist. The replacement of three arginine residues by alanines in the M-Twist basic domain was sufficient to abolish both the binding and inhibition of MyoD by M-Twist, while the domain retained other M-Twist functions such as heterodimerization with an E protein and inhibition of MEF2 transactivation. These findings demonstrate that M-Twist interacts with MyoD through the basic domains, thereby inhibiting MyoD.
34
Delfini, M., E. Hirsinger, O. Pourquie, and D. Duprez. "Delta 1-activated notch inhibits muscle differentiation without affecting Myf5 and Pax3 expression in chick limb myogenesis." Development 127, no. 23 (December 1, 2000): 5213–24. http://dx.doi.org/10.1242/dev.127.23.5213.
Full textAbstract:
The myogenic basic helix-loop-helix (bHLH) transcription factors, Myf5, MyoD, myogenin and MRF4, are unique in their ability to direct a program of specific gene transcription leading to skeletal muscle phenotype. The observation that Myf5 and MyoD can force myogenic conversion in non-muscle cells in vitro does not imply that they are equivalent. In this paper, we show that Myf5 transcripts are detected before those of MyoD during chick limb development. The Myf5 expression domain resembles that of Pax3 and is larger than that of MyoD. Moreover, Myf5 and Pax3 expression is correlated with myoblast proliferation, while MyoD is detected in post-mitotic myoblasts. These data indicate that Myf5 and MyoD are involved in different steps during chick limb bud myogenesis, Myf5 acting upstream of MyoD. The progression of myoblasts through the differentiation steps must be carefully controlled to ensure myogenesis at the right place and time during wing development. Because Notch signalling is known to prevent differentiation in different systems and species, we sought to determine whether these molecules regulate the steps occurring during chick limb myogenesis. Notch1 transcripts are associated with immature myoblasts, while cells expressing the ligands Delta1 and Serrate2 are more advanced in myogenesis. Misexpression of Delta1 using a replication-competent retrovirus activates the Notch pathway. After activation of this pathway, myoblasts still express Myf5 and Pax3 but have downregulated MyoD, resulting in inhibition of terminal muscle differentiation. We conclude that activation of Notch signalling during chick limb myogenesis prevents Myf5-expressing myoblasts from progressing to the MyoD-expressing stage.
35
Kablar, B., K. Krastel, C. Ying, A. Asakura, S. J. Tapscott, and M. A. Rudnicki. "MyoD and Myf-5 differentially regulate the development of limb versus trunk skeletal muscle." Development 124, no. 23 (December 1, 1997): 4729–38. http://dx.doi.org/10.1242/dev.124.23.4729.
Full textAbstract:
The myogenic progenitors of epaxial (paraspinal and intercostal) and hypaxial (limb and abdominal wall) musculature are believed to originate in dorsal-medial and ventral-lateral domains, respectively, of the developing somite. To investigate the hypothesis that Myf-5 and MyoD have different roles in the development of epaxial and hypaxial musculature, we further characterized myogenesis in Myf-5- and MyoD-deficient embryos by several approaches. We examined expression of a MyoD-lacZ transgene in Myf-5 and MyoD mutant embryos to characterize the temporal-spatial patterns of myogenesis in mutant embryos. In addition, we performed immunohistochemistry on sectioned Myf-5 and MyoD mutant embryos with antibodies reactive with desmin, nestin, myosin heavy chain, sarcomeric actin, Myf-5, MyoD and myogenin. While MyoD(−/−) embryos displayed normal development of paraspinal and intercostal muscles in the body proper, muscle development in limb buds and brachial arches was delayed by about 2.5 days. By contrast, Myf-5(−/−) embryos displayed normal muscle development in limb buds and brachial arches, and markedly delayed development of paraspinal and intercostal muscles. Although MyoD mutant embryos exhibited delayed development of limb musculature, normal migration of Pax-3-expressing cells into the limb buds and normal subsequent induction of Myf-5 in myogenic precursors was observed. These results suggest that Myf-5 expression in the limb is insufficient for the normal progression of myogenic development. Taken together, these observations strongly support the hypothesis that Myf-5 and MyoD play unique roles in the development of epaxial and hypaxial muscle, respectively.
36
Polesskaya, Anna, Irina Naguibneva, Arnaud Duquet, Eyal Bengal, Philippe Robin, and Annick Harel-Bellan. "Interaction between Acetylated MyoD and the Bromodomain of CBP and/or p300." Molecular and Cellular Biology 21, no. 16 (August 15, 2001): 5312–20. http://dx.doi.org/10.1128/mcb.21.16.5312-5320.2001.
Full textAbstract:
ABSTRACT Acetylation is emerging as a posttranslational modification of nuclear proteins that is essential to the regulation of transcription and that modifies transcription factor affinity for binding sites on DNA, stability, and/or nuclear localization. Here, we present both in vitro and in vivo evidence that acetylation increases the affinity of myogenic factor MyoD for acetyltransferases CBP and p300. In myogenic cells, the fraction of endogenous MyoD that is acetylated was found associated with CBP or p300. In vitro, the interaction between MyoD and CBP was more resistant to high salt concentrations and was detected with lower doses of MyoD when MyoD was acetylated. Interestingly, an analysis of CBP mutants revealed that the interaction with acetylated MyoD involves the bromodomain of CBP. In live cells, MyoD mutants that cannot be acetylated did not associate with CBP or p300 and were strongly impaired in their ability to cooperate with CBP for transcriptional activation of a muscle creatine kinase-luciferase construct. Taken together, our data suggest a new mechanism for activation of protein function by acetylation and demonstrate for the first time an acetylation-dependent interaction between the bromodomain of CBP and a nonhistone protein.
37
L'honore, Aurore, Vanessa Rana, Nikola Arsic, Celine Franckhauser, Ned J. Lamb, and Anne Fernandez. "Identification of a New Hybrid Serum Response Factor and Myocyte Enhancer Factor 2-binding Element in MyoD Enhancer Required for MyoD Expression during Myogenesis." Molecular Biology of the Cell 18, no. 6 (June 2007): 1992–2001. http://dx.doi.org/10.1091/mbc.e06-09-0867.
Full textAbstract:
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.
38
Gerhart, Jacquelyn, Christine Neely, Justin Elder, Jessica Pfautz, Jordanna Perlman, Luis Narciso, Kersti K. Linask, Karen Knudsen, and Mindy George-Weinstein. "Cells that express MyoD mRNA in the epiblast are stably committed to the skeletal muscle lineage." Journal of Cell Biology 178, no. 4 (August 13, 2007): 649–60. http://dx.doi.org/10.1083/jcb.200703060.
Full textAbstract:
The epiblast of the chick embryo contains cells that express MyoD mRNA but not MyoD protein. We investigated whether MyoD-positive (MyoDpos) epiblast cells are stably committed to the skeletal muscle lineage or whether their fate can be altered in different environments. A small number of MyoDpos epiblast cells were tracked into the heart and nervous system. In these locations, they expressed MyoD mRNA and some synthesized MyoD protein. No MyoDpos epiblast cells differentiated into cardiac muscle or neurons. Similar results were obtained when MyoDpos cells were isolated from the epiblast and microinjected into the precardiac mesoderm or neural plate. In contrast, epiblast cells lacking MyoD differentiated according to their environment. These results demonstrate that the epiblast contains both multipotent cells and a subpopulation of cells that are stably committed to the skeletal muscle lineage before the onset of gastrulation. Stable programming in the epiblast may ensure that MyoDpos cells express similar signaling molecules in a variety of environments.
39
Gerber, A. N., and S. J. Tapscott. "Tumor cell complementation groups based on myogenic potential: evidence for inactivation of loci required for basic helix-loop-helix protein activity." Molecular and Cellular Biology 16, no. 7 (July 1996): 3901–8. http://dx.doi.org/10.1128/mcb.16.7.3901.
Full textAbstract:
Basic helix-loop-helix (bHLH) proteins mediate terminal differentiation in many lineages. By using the bHLH protein MyoD, which can dominantly activate the myogenic differentiation program in numerous cell types, we demonstrated that recessive defects in bHLH protein function are present in human tumor lines. In contrast to prior work with primary cell cultures, MyoD did not activate the myogenic program in six of the eight tumor lines we tested. Cell fusions between the MyoD-defective lines and fibroblasts restored MyoD activity, indicating that the deficiency of a gene or factor prevents bHLH protein function in the tumor lines. Fusions between certain pairings of the MyoD-defective lines also restored MyoD activity, allowing the tumor lines to be assigned to complementation groups on the basis of their ability to execute the myogenic program and indicating that multiple mechanisms exist for abrogation of bHLH protein activity. These groups provide a basis for identifying genes critical for bHLH-mediated differentiation and tumor progression by using genetic complementation.
40
Park, Sooyeon, Jung-Sook Lee, Keun-Chul Lee, and Jung-Hoon Yoon. "Formosa undariae sp. nov., isolated from a reservoir containing the brown algae Undaria pinnatifida." International Journal of Systematic and Evolutionary Microbiology 63, Pt_11 (November 1, 2013): 4130–35. http://dx.doi.org/10.1099/ijs.0.053157-0.
Full textAbstract:
A strain of Gram-staining-negative, aerobic, non-flagellated, non-gliding and rod-shaped bacteria, designated WS-MY3T, was isolated from a brown algae reservoir in South Korea. Strain WS-MY3T grew optimally at 25 °C, at pH 7.0–8.0 and in the presence of 2.0–3.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences showed that strain WS-MY3T fell within the cluster comprising the type strains of species of the genus Formosa , clustering coherently with the type strains of Formosa agariphila and Formosa algae . It exhibited 16S rRNA gene sequence similarity values of 98.7, 97.9 and 96.8 % to the type strains of F. agariphila, F. algae and Formosa spongicola , respectively. Strain WS-MY3T contained MK-6 as the predominant menaquinone and iso-C15 : 0, iso-C16 : 0 3-OH, iso-C15 : 1 G and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) as the major fatty acids. The major polar lipids of strain WS-MY3T were phosphatidylethanolamine and two unidentified lipids. The DNA G+C content of strain WS-MY3T was 37.3 mol% and its DNA–DNA relatedness values with F. agariphila KCTC 12365T and F. algae KCTC 12364T were 23 % and 17 %, respectively. The phylogenetic and genetic distinctiveness and differential phenotypic properties revealed that strain WS-MY3T is separate from the three recognized species of the genus Formosa . On the basis of the data presented, strain WS-MY3T is considered to represent a novel species of the genus Formosa , for which the name Formosa undariae sp. nov. is proposed. The type strain is WS-MY3T ( = KCTC 32328T = CECT 8286T).
41
Yoshida, N., S. Yoshida, K. Koishi, K. Masuda, and Y. Nabeshima. "Cell heterogeneity upon myogenic differentiation: down-regulation of MyoD and Myf-5 generates ‘reserve cells’." Journal of Cell Science 111, no. 6 (March 15, 1998): 769–79. http://dx.doi.org/10.1242/jcs.111.6.769.
Full textAbstract:
When a proliferating myoblast culture is induced to differentiate by deprivation of serum in the medium, a significant proportion of cells escape from terminal differentiation, while the rest of the cells differentiate. Using C2C12 mouse myoblast cells, this heterogeneity observed upon differentiation was investigated with an emphasis on the myogenic regulatory factors. The differentiating part of the cell population followed a series of well-described events, including expression of myogenin, p21(WAF1), and contractile proteins, permanent withdrawal from the cell cycle and cell fusion, whereas the rest of the cells did not initiate any of these events. Interestingly, the latter cells showed an undetectable or greatly reduced level of MyoD and Myf-5 expression, which had been originally expressed in the undifferentiated proliferating myoblasts. When these undifferentiated cells were isolated and returned to the growth conditions, they progressed through the cell cycle and regained MyoD expression. These cells demonstrated identical features with the original culture on the deprivation of serum. They produced both MyoD-positive differentiating and MyoD-negative undifferentiated populations once again. Thus the undifferentiated cells in the serum-deprived culture were designated ‘reserve cells’. Upon serum deprivation, MyoD expression rapidly decreased as a result of down-regulation in approximately 50% of the cells. After this heterogenization, MyoD positive cells expressed myogenin, which is the earliest known event of terminal differentiation and marks irreversible commitment to this, while MyoD-negative cells did not differentiate and became the reserve cells. We also demonstrated that ectopic expression of MyoD converted the reserve cells to differentiating cells, indicating that down-regulation of MyoD is a causal event in the formation of reserve cells.
42
Lin, Yung-Jui, Chien-Han Kao, Sheng-Pin Hsiao, and Shen-Liang Chen. "The cooperation of cis-elements during M-cadherin promoter activation." Biochemical Journal 478, no. 4 (February 26, 2021): 911–26. http://dx.doi.org/10.1042/bcj20200535.
Full textAbstract:
M-cadherin is a skeletal muscle-specific transmembrane protein mediating the cell-cell adhesion of myoblasts during myogenesis. It is expressed in the proliferating satellite cells and highly induced by myogenic regulatory factors (MRFs) during terminal myogenic differentiation. Several conserved cis-elements, including 5 E-boxes, 2 GC boxes, and 1 conserved downstream element (CDE) were identified in the M-cadherin proximal promoter. We found that E-box-3 and -4 close to the transcription initiation site (TIS) mediated most of its transactivation by MyoD, the strongest myogenic MRF. Including of any one of the other E-boxes restored the full activation by MyoD, suggesting an essential collaboration between E-boxes. Stronger activation of M-cadherin promoter than that of muscle creatine kinase (MCK) by MyoD was observed regardless of culture conditions and the presence of E47. Furthermore, MyoD/E47 heterodimer and MyoD ∼ E47 fusion protein achieved similar levels of activation in differentiation medium (DM), suggesting high affinity of MyoD/E47 to E-boxes 3/4 under DM. We also found that GC boxes and CDE positively affected MyoD mediated activation. The CDE element was predicted to be the target of the chromatin-modifying factor Meis1/Pbx1 heterodimer. Knockdown of Pbx1 significantly reduced the expression level of M-cadherin, but increased that of N-cadherin. Using ChIP assay, we further found significant reduction in MyoD recruitment to M-cadherin promoter when CDE was deleted. Taken together, these observations suggest that the chromatin-modifying function of Pbx1/Meis1 is critical to M-cadherin promoter activation before MyoD is recruited to E-boxes to trigger transcription.
43
Anderson, Judy E., Laura M. McIntosh, Andrea N. Moor (neé Pernitsky), and Zipora Yablonka–Reuveni. "Levels of MyoD Protein Expression Following Injury of mdx and Normal Limb Muscle Are Modified by Thyroid Hormone." Journal of Histochemistry & Cytochemistry 46, no. 1 (January 1998): 59–67. http://dx.doi.org/10.1177/002215549804600108.
Full textAbstract:
Thyroid hormone (T3) affects muscle development and muscle regeneration. It also interacts with the muscle regulatory gene MyoD in culture and affects myoblast proliferation. We studied the localization of MyoD protein using a well-characterized polyclonal antibody for immunohistochemistry. Relative numbers of myogenic precursor cells per field were identified by their MyoD expression during muscle regeneration in normal and mdx dystrophic mice, with particular reference to the expression in mononuclear cells and myotubes at various T3 levels. In regeneration by normal muscles, relatively few MyoD+ nuclei per field were present in mononuclear cells of euthyroid and hypothyroid mice. MyoD staining of mononuclear cell nuclei was approximately doubled in fields of regenerating muscles of normal hyperthyroid compared to euthyroid mice, and was observed in precursors that appeared to be aligned before fusion into myotubes. In mdx regenerating muscle, twofold more mononuclear cells positive for MyoD were present in all three treatment groups compared to normal muscles regenerating under the same conditions. Localization was similar to the pattern in normal euthyroid mice. However, in muscles regenerating in hyperthyroid mdx mice, both mononuclear cell nuclei and centrally located nuclei in a subpopulation (about 15%) of new myotubes formed after the crush injury were intensely stained for MyoD protein. The changes observed are consistent with reports on T3-induced alteration of muscle repair, and propose a link between MyoD regulation and the accelerated differentiation during regeneration under high T3 conditions.
44
Sartorelli, V., J. Huang, Y. Hamamori, and L. Kedes. "Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C." Molecular and Cellular Biology 17, no. 2 (February 1997): 1010–26. http://dx.doi.org/10.1128/mcb.17.2.1010.
Full textAbstract:
By searching for molecules that assist MyoD in converting fibroblasts to muscle cells, we have found that p300 and CBP, two related molecules that act as transcriptional adapters, coactivate the myogenic basic-helix-loop-helix (bHLH) proteins. Coactivation by p300 involves novel physical interactions between p300 and the amino-terminal activation domain of MyoD. In particular, disruption of the FYD domain, a group of three amino acids conserved in the activation domains of other myogenic bHLH proteins, drastically diminishes the transactivation potential of MyoD and abolishes both p300-mediated coactivation and the physical interaction between MyoD and p300. Two domains of p300, at its amino and carboxy terminals, independently function to both mediate coactivation and physically interact with MyoD. A truncated segment of p300, unable to bind MyoD, acts as a dominant negative mutation and abrogates both myogenic conversion and transactivation by MyoD, suggesting that endogenous p300 is a required coactivator for MyoD function. The p300 dominant negative peptide forms multimers with intact p300. p300 and CBP serve as coactivators of another class of transcriptional activators critical for myogenesis, myocyte enhancer factor 2 (MEF2). In fact, transactivation mediated by the MEF2C protein is potentiated by the two coactivators, and this phenomenon is associated with the ability of p300 to interact with the MADS domain of MEF2C. Our results suggest that p300 and CBP may positively influence myogenesis by reinforcing the transcriptional autoregulatory loop established between the myogenic bHLH and the MEF2 factors.
45
Kablar, Boris, Atsushi Asakura, Kirsten Krastel, Chuyan Ying, Linda L. May, David J. Goldhamer, and Michael A. Rudnicki. "MyoD and Myf-5 define the specification of musculature of distinct embryonic origin." Biochemistry and Cell Biology 76, no. 6 (December 1, 1998): 1079–91. http://dx.doi.org/10.1139/o98-107.
Full textAbstract:
Mounting evidence supports the notion that Myf-5 and MyoD play unique roles in the development of epaxial (originating in the dorso-medial half of the somite, e.g. back muscles) and hypaxial (originating in the ventro-lateral half of the somite, e.g. limb and body wall muscles) musculature. To further understand how Myf-5 and MyoD genes co-operate during skeletal muscle specification, we examined and compared the expression pattern of MyoD-lacZ (258/-2.5lacZ and MD6.0-lacZ) transgenes in wild-type, Myf-5, and MyoD mutant embryos. We found that the delayed onset of muscle differentiation in the branchial arches, tongue, limbs, and diaphragm of MyoD-/- embryos was a consequence of a reduced ability of myogenic precursor cells to progress through their normal developmental program and not because of a defect in migration of muscle progenitor cells into these regions. We also found that myogenic precursor cells for back, intercostal, and abdominal wall musculature in Myf-5-/-embryos failed to undergo normal translocation or differentiation. By contrast, the myogenic precursors of intercostal and abdominal wall musculature in MyoD-/- embryos underwent normal translocation but failed to undergo timely differentiation. In conclusion, these observations strongly support the hypothesis that Myf-5 plays a unique role in the development of muscles arising after translocation of epithelial dermamyotome cells along the medial edge of the somite to the subjacent myotome (e.g., back or epaxial muscle) and that MyoD plays a unique role in the development of muscles arising from migratory precursor cells (e.g., limb and branchial arch muscles, tongue, and diaphragm). In addition, the expression pattern of MyoD-lacZ transgenes in the intercostal and abdominal wall muscles of Myf-5-/- and MyoD-/- embryos suggests that appropriate development of these muscles is dependent on both genes and, therefore, these muscles have a dual embryonic origin (epaxial and hypaxial).Key words: epaxial and hypaxial muscle, Myf-5, MyoD, mouse development, somite.
46
Carnac, Gilles, Michael Primig, Magali Kitzmann, Philippe Chafey, David Tuil, Ned Lamb, and Anne Fernandez. "RhoA GTPase and Serum Response Factor Control Selectively the Expression of MyoD without Affecting Myf5 in Mouse Myoblasts." Molecular Biology of the Cell 9, no. 7 (July 1998): 1891–902. http://dx.doi.org/10.1091/mbc.9.7.1891.
Full textAbstract:
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.
47
Weintraub, Michael, Thea Kalebic, Lee J. Helman, and Kishor G. Bhatia. "Disruption of the MyoD/p21 Pathway in Rhabdomyosarcoma." Sarcoma 1, no. 3-4 (1997): 135–41. http://dx.doi.org/10.1080/13577149778218.
Full textAbstract:
Purpose. Rhabdomyosarcoma (RMS) is an embryonal tumor thought to arise from skeletal muscle cells that fail to differentiate terminally. The majority of RMSs express MyoD, a protein essential to the differentiation of skeletal muscle. It was recently shown that during myogenesis, MyoD activates the expression of the cyclin-dependent kinase inhibitor (CDKi), p21, which itself plays a critical role in normal muscle development. To investigate the integrity of the MyoD/p21 pathway in RMS, we analyzed p21 and its relationship to MyoD expression in RMS.Methods. A panel of RMS samples was assembled from primary biopsies and from cell lines. Integrity of p21 was analyzed by single-strand conformation polymorphism (SSCP) and sequencing. Expression of p21 and MyoD was determined by Northern blot analysis, and the ability of exogenous p21 to arrest the cell cycle of RMS cell line was determined by transfection studies.Results. Our analysis indicates that although p21 is wild type in RMS, there is an inverse correlation between the levels of p21 and MyoD in these tumors. Tumors that express significant amounts of MyoD fail to express p21. This does not appear to be the result of mutations within the potential CACGTG sites present in the p21 promoter region or in the coding region of p21. An additional group of RMSs express very high levels of p21 but express little, if any, MyoD. Furthermore, RD, a RMS cell line which expresses high levels of endogenous p21, undergoes withdrawal from the cell cycle following forced expression of p21, suggesting that the pathway which would lead to G1arrest from endogenous p21 activity is defective.Discussion. These data suggest that the interaction between p21 and MyoD is defective in RMS although the precise nature of the defect remains to be elucidated.
48
de la Serna, Ivana L., Yasuyuki Ohkawa, Charlotte A. Berkes, Donald A. Bergstrom, Caroline S. Dacwag, Stephen J. Tapscott, and Anthony N. Imbalzano. "MyoD Targets Chromatin Remodeling Complexes to the Myogenin Locus Prior to Forming a Stable DNA-Bound Complex." Molecular and Cellular Biology 25, no. 10 (May 15, 2005): 3997–4009. http://dx.doi.org/10.1128/mcb.25.10.3997-4009.2005.
Full textAbstract:
ABSTRACT The activation of muscle-specific gene expression requires the coordinated action of muscle regulatory proteins and chromatin-remodeling enzymes. Microarray analysis performed in the presence or absence of a dominant-negative BRG1 ATPase demonstrated that approximately one-third of MyoD-induced genes were highly dependent on SWI/SNF enzymes. To understand the mechanism of activation, we performed chromatin immunoprecipitations analyzing the myogenin promoter. We found that H4 hyperacetylation preceded Brg1 binding in a MyoD-dependent manner but that MyoD binding occurred subsequent to H4 modification and Brg1 interaction. In the absence of functional SWI/SNF enzymes, muscle regulatory proteins did not bind to the myogenin promoter, thereby providing evidence for SWI/SNF-dependent activator binding. We observed that the homeodomain factor Pbx1, which cooperates with MyoD to stimulate myogenin expression, is constitutively bound to the myogenin promoter in a SWI/SNF-independent manner, suggesting a two-step mechanism in which MyoD initially interacts indirectly with the myogenin promoter and attracts chromatin-remodeling enzymes, which then facilitate direct binding by MyoD and other regulatory proteins.
49
Rawls, Alan, and Eric N. Olson. "MyoD Meets Its Maker." Cell 89, no. 1 (April 1997): 5–8. http://dx.doi.org/10.1016/s0092-8674(00)80175-0.
Full text
50
Parmacek, Michael S. "Myocardin—Not Quite MyoD." Arteriosclerosis, Thrombosis, and Vascular Biology 24, no. 9 (September 2004): 1535–37. http://dx.doi.org/10.1161/01.atv.0000141044.03875.7f.
Full text