A model for the modulation of muscle cell determination and differentiation by growth factors

1989 ◽  
Vol 67 (9) ◽  
pp. 575-580 ◽  
Author(s):  
David J. Kelvin ◽  
Terry P. Yamaguchi ◽  
Gilles Simard ◽  
Helen H. Tai ◽  
Andrew I. Sue-A-Quan ◽  
...  
Keyword(s):  
Growth Factors ◽  
Muscle Cell ◽  
Nuclear Dna ◽  
Regulatory Sequences ◽  
Cis Acting ◽  
Muscle Gene Expression ◽  
Muscle Genes ◽  
Adult Organism ◽  
Muscle Gene

In an adult organism three principal types of muscle tissue can be found: skeletal, smooth, and cardiac. While each display subtle differences, for the most part they express a common set of genes that are representative of differentiated muscle. Several in vitro muscle cell lines have provided clues as to how the developmental programs of muscle cell proliferation, determination, and differentiation are controlled. In this paper we will explore recent advances in our understanding of how growth factors, acting through specific signal transduction pathways, control muscle gene expression. The transcription of muscle genes is controlled by specific cis-acting regulatory sequences. We will discuss how growth factors may exert their effects on muscle genes by modulating the expression of nuclear DNA-binding proteins that directly regulate muscle gene expression.Key words: determination, myogenesis, oncogene, fibroblast growth factor, myoD1.

scholarly journals Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245618
Author(s):  
Abhinav Adhikari ◽  
William Kim ◽  
Judith Davie
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Gene Activation ◽  
Gene Promoters ◽  
Muscle Gene Expression ◽  
Transcription Machinery ◽  
Muscle Genes ◽  
Muscle Gene

Skeletal muscle gene expression is governed by the myogenic regulatory family (MRF) which includes MyoD (MYOD1) and myogenin (MYOG). MYOD1 and MYOG are known to regulate an overlapping set of muscle genes, but MYOD1 cannot compensate for the absence of MYOG in vivo. In vitro, late muscle genes have been shown to be bound by both factors, but require MYOG for activation. The molecular basis for this requirement was unclear. We show here that MYOG is required for the recruitment of TBP and RNAPII to muscle gene promoters, indicating that MYOG is essential in assembling the transcription machinery. Genes regulated by MYOD1 and MYOG include genes required for muscle fusion, myomaker and myomerger, and we show that myomaker is fully dependent on activation by MYOG. We also sought to determine the role of MYOD1 in MYOG dependent gene activation and unexpectedly found that MYOG is required to maintain Myod1 expression. However, we also found that exogenous MYOD1 was unable to compensate for the loss of Myog and activate muscle gene expression. Thus, our results show that MYOD1 and MYOG act in a feed forward loop to maintain each other’s expression and also show that it is MYOG, and not MYOD1, that is required to load TBP and activate gene expression on late muscle gene promoters bound by both factors.

TGFβ-1 and epithelial-mesenchymal interactions promote smooth muscle gene expression in bone marrow stromal cells: Possible application in therapies for urological defects

2008 ◽  
Vol 31 (11) ◽  
pp. 951-959 ◽  
Author(s):  
C. Becker ◽  
T. Laeufer ◽  
J. Arikkat ◽  
G. Jakse
Keyword(s):  
Bone Marrow ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Smooth Muscle Actin ◽  
Muscle Actin ◽  
Muscle Gene Expression ◽  
Muscle Gene

Purpose For regenerative and cellular therapies of the urinary tract system, autologous bladder smooth muscle cells (SMCs) have several limitations, including constricted in vitro proliferation capacity and, more importantly, inability to be used in malignant conditions. The use of in vitro (pre-)differentiated multipotential adult progenitor cells may help to overcome the shortcomings associated with primary cells. Methods By mimicking environmental conditions of the bladder wall, we investigated in vitro effects of growth factor applications and epithelial-mesenchymal interactions on smooth muscle gene expression and on the morphological appearance of adherent bone marrow stromal cells (BMSCs). Results Transcription growth factor beta-1 (TGFβ-1) upregulated the transcription of myogenic gene desmin and smooth muscle actin-γ2 in cultured BMSCs. Stimulatory effects were significantly increased by coculture with urothelial cells. Prolonged stimulation times and epigenetic modifications further enhanced transcription levels, indicating a dose-response relationship. Immunocytochemical staining of in vitro-differentiated BMSCs revealed expression of myogenic protein α-smooth muscle actin and desmin, and changes in morphological appearance from a fusiform convex shape to a laminar flattened shape with filamentous inclusions similar to the appearance of bladder SMCs. In contrast to the TGFβ-1 action, application of vascular endothelial growth factor (VEGF) did not affect the cells. Conclusions The combined application of TGFβ-1 and epithelial-mesenchymal interactions promoted in vitro outgrowth of cells with a smooth muscle-like phenotype from a selected adherent murine bone marrow-derived cell population.

scholarly journals Skeletal muscle reprogramming by breast cancer regardless of treatment history or tumor molecular subtype

2019 ◽  
Author(s):  
Hannah E. Wilson ◽  
David A. Stanton ◽  
Cortney Montgomery ◽  
Aniello M. Infante ◽  
Matthew Taylor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Molecular Subtype ◽  
Clinical History ◽  
Muscle Gene Expression ◽  
Treatment History ◽  
Muscle Gene

ABSTRACTIncreased susceptibility to fatigue is a negative predictor of survival commonly experienced by women with breast cancer. Here, we sought to identify molecular changes induced in human skeletal muscle by BC regardless of treatment history or tumor molecular subtype using RNA-sequencing and proteomic analyses. Mitochondrial dysfunction was apparent across all molecular subtypes, with the greatest degree of transcriptomic changes occurring in women with HER2/neu-overexpressing tumors, though muscle from patients of all subtypes exhibited similar pathway-level dysregulation. Interestingly, we found no relationship between anti-cancer treatments and muscle gene expression, suggesting that fatigue is a product of BC per se rather than clinical history. In vitro and in vivo experimentation confirmed the ability of BC cells to alter mitochondrial function and ATP content in muscle. These data suggest that interventions supporting muscle in the presence of BC-induced mitochondrial dysfunction may alleviate fatigue and improve the lives of women with BC.

Tumor necrosis factor inhibits human myogenesis in vitro

1988 ◽  
Vol 8 (6) ◽  
pp. 2295-2301
Author(s):  
S C Miller ◽  
H Ito ◽  
H M Blau ◽  
F M Torti
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Myoblast Differentiation ◽  
Specific Gene ◽  
Necrosis Factor Alpha ◽  
Muscle Gene Expression ◽  
Muscle Gene ◽  
Necrosis Factor

We examined the effects of human recombinant tumor necrosis factor-alpha (TNF) on human primary myoblasts. When added to proliferating myoblasts, TNF inhibited the expression of alpha-cardiac actin, a muscle-specific gene whose expression is observed at low levels in human myoblasts. TNF also inhibited muscle differentiation as measured by several parameters, including cell fusion and the expression of other muscle-specific genes, such as alpha-skeletal actin and myosin heavy chain. Muscle cells were sensitive to TNF in a narrow temporal window of differentiation. Northern (RNA) blot and immunofluorescence analyses revealed that human muscle gene expression became unresponsive to TNF coincident with myoblast differentiation. When TNF was added to differentiated myotubes, there was no effect on muscle gene expression. In contrast, TNF-inducible mRNAs such as interferon beta-2 still responded, suggesting that the signal mediated by TNF binding to its receptor had no effect on muscle-specific genes after differentiation.

Multiple hormone-inducible enhancers as mediators of differential transcription

1986 ◽  
Vol 6 (12) ◽  
pp. 4526-4538
Author(s):  
M G Toohey ◽  
K L Morley ◽  
D O Peterson
Keyword(s):  
Regulatory Control ◽  
Regulatory Sequences ◽  
Enhancer Element ◽  
Cis Acting ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Differential Transcription ◽  
Virus Promoter ◽  
Inducible Gene

Sets of genes under a common regulatory control in a given cell type are often differentially transcribed. The possibility that this differential transcription can be modulated by the number or strength of cis-acting regulatory sequences associated with a given gene was tested by using the glucocorticoid-responsive enhancer element associated with the mouse mammary tumor virus promoter. Results indicate that differential levels of hormone-inducible gene expression can be modulated in an additive way by the number of glucocorticoid-responsive enhancers associated with this promoter. Realization of these effects shows little preference for position of the additional elements with respect to the promoter. When sequences that bind the glucocorticoid receptor in vitro with somewhat lower affinity than the enhancer were tested, these additive effects were not detected. The results support that differential transcription of genes subject to a common regulatory control can be mediated, at least in part, by the number or strength of their associated cis-acting regulatory sequences.

scholarly journals Multiple hormone-inducible enhancers as mediators of differential transcription.

1986 ◽  
Vol 6 (12) ◽  
pp. 4526-4538 ◽  
Author(s):  
M G Toohey ◽  
K L Morley ◽  
D O Peterson
Keyword(s):  
Regulatory Control ◽  
Regulatory Sequences ◽  
Enhancer Element ◽  
Cis Acting ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Differential Transcription ◽  
Virus Promoter ◽  
Inducible Gene

Sets of genes under a common regulatory control in a given cell type are often differentially transcribed. The possibility that this differential transcription can be modulated by the number or strength of cis-acting regulatory sequences associated with a given gene was tested by using the glucocorticoid-responsive enhancer element associated with the mouse mammary tumor virus promoter. Results indicate that differential levels of hormone-inducible gene expression can be modulated in an additive way by the number of glucocorticoid-responsive enhancers associated with this promoter. Realization of these effects shows little preference for position of the additional elements with respect to the promoter. When sequences that bind the glucocorticoid receptor in vitro with somewhat lower affinity than the enhancer were tested, these additive effects were not detected. The results support that differential transcription of genes subject to a common regulatory control can be mediated, at least in part, by the number or strength of their associated cis-acting regulatory sequences.

scholarly journals Modulation of Smooth Muscle Gene Expression by Association of Histone Acetyltransferases and Deacetylases with Myocardin

2005 ◽  
Vol 25 (1) ◽  
pp. 364-376 ◽  
Author(s):  
Dongsun Cao ◽  
Zhigao Wang ◽  
Chun-Li Zhang ◽  
Jiyeon Oh ◽  
Weibing Xing ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Transcriptional Activation ◽  
Histone Deacetylases ◽  
Serum Response Factor ◽  
Gene Activation ◽  
Muscle Gene Expression ◽  
P300 Binding ◽  
Muscle Genes ◽  
Muscle Gene

ABSTRACT Differentiation of smooth muscle cells is accompanied by the transcriptional activation of an array of muscle-specific genes controlled by serum response factor (SRF). Myocardin is a cardiac and smooth muscle-specific expressed transcriptional coactivator of SRF and is sufficient and necessary for smooth muscle gene expression. Here, we show that myocardin induces the acetylation of nucleosomal histones surrounding SRF-binding sites in the control regions of smooth muscle genes. The promyogenic activity of myocardin is enhanced by p300, a histone acetyltransferase that associates with the transcription activation domain of myocardin. Conversely, class II histone deacetylases interact with a domain of myocardin distinct from the p300-binding domain and suppress smooth muscle gene activation by myocardin. These findings point to myocardin as a nexus for positive and negative regulation of smooth muscle gene expression by changes in chromatin acetylation.

scholarly journals Tumor necrosis factor inhibits human myogenesis in vitro.

1988 ◽  
Vol 8 (6) ◽  
pp. 2295-2301 ◽  
Author(s):  
S C Miller ◽  
H Ito ◽  
H M Blau ◽  
F M Torti
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Myoblast Differentiation ◽  
Specific Gene ◽  
Necrosis Factor Alpha ◽  
Muscle Gene Expression ◽  
Muscle Gene ◽  
Necrosis Factor

We examined the effects of human recombinant tumor necrosis factor-alpha (TNF) on human primary myoblasts. When added to proliferating myoblasts, TNF inhibited the expression of alpha-cardiac actin, a muscle-specific gene whose expression is observed at low levels in human myoblasts. TNF also inhibited muscle differentiation as measured by several parameters, including cell fusion and the expression of other muscle-specific genes, such as alpha-skeletal actin and myosin heavy chain. Muscle cells were sensitive to TNF in a narrow temporal window of differentiation. Northern (RNA) blot and immunofluorescence analyses revealed that human muscle gene expression became unresponsive to TNF coincident with myoblast differentiation. When TNF was added to differentiated myotubes, there was no effect on muscle gene expression. In contrast, TNF-inducible mRNAs such as interferon beta-2 still responded, suggesting that the signal mediated by TNF binding to its receptor had no effect on muscle-specific genes after differentiation.

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