scholarly journals Expression of muscle genes in heterokaryons depends on gene dosage.

1986 ◽  
Vol 102 (1) ◽  
pp. 124-130 ◽  
Author(s):  
G K Pavlath ◽  
H M Blau
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Gene Dosage ◽  
Cell Types ◽  
Threshold Concentration ◽  
Specific Gene ◽  
Mouse Muscle ◽  
Muscle Gene Expression ◽  
Muscle Genes ◽  
Muscle Gene

We report that gene dosage, or the ratio of nuclei from two cell types fused to form a heterokaryon, affects the time course of differentiation-specific gene expression. The rate of appearance of the human muscle antigen, 5.1H11, is significantly faster in heterokaryons with equal or near-equal numbers of mouse muscle and human fibroblast nuclei than in heterokaryons with increased numbers of nuclei from either cell type. By 4 d after fusion, a high frequency of gene expression is evident at all ratios and greater than 75% of heterokaryons express the antigen even when the nonmuscle nuclei greatly outnumber the muscle nuclei. The kinetic differences observed with different nuclear ratios suggest that the concentration of putative trans-acting factors significantly influences the rate of muscle gene expression: a threshold concentration is necessary, but an excess may be inhibitory.

scholarly journals TBP/TFIID-dependent activation of MyoD target genes in skeletal muscle cells

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Barbora Malecova ◽  
Alessandra Dall'Agnese ◽  
Luca Madaro ◽  
Sole Gatto ◽  
Paula Coutinho Toto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Control Cell ◽  
Myoblast Differentiation ◽  
Specific Gene ◽  
Specific Gene Expression ◽  
Muscle Gene Expression ◽  
Primary Mouse ◽  
Muscle Genes ◽  
Muscle Gene

Change in the identity of the components of the transcription pre-initiation complex is proposed to control cell type-specific gene expression. Replacement of the canonical TFIID-TBP complex with TRF3/TBP2 was reported to be required for activation of muscle-gene expression. The lack of a developmental phenotype in TBP2 null mice prompted further analysis to determine whether TBP2 deficiency can compromise adult myogenesis. We show here that TBP2 null mice have an intact regeneration potential upon injury and that TBP2 is not expressed in established C2C12 muscle cell or in primary mouse MuSCs. While TFIID subunits and TBP are downregulated during myoblast differentiation, reduced amounts of these proteins form a complex that is detectable on promoters of muscle genes and is essential for their expression. This evidence demonstrates that TBP2 does not replace TBP during muscle differentiation, as previously proposed, with limiting amounts of TFIID-TBP being required to promote muscle-specific gene expression.

scholarly journals Age and Sex-Dependent ADNP Regulation of Muscle Gene Expression Is Correlated with Motor Behavior: Possible Feedback Mechanism with PACAP

2020 ◽  
Vol 21 (18) ◽  
pp. 6715 ◽  
Author(s):  
Oxana Kapitansky ◽  
Shlomo Sragovich ◽  
Iman Jaljuli ◽  
Adva Hadar ◽  
Eliezer Giladi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Muscle Development ◽  
Motor Behavior ◽  
Expression Patterns ◽  
Feedback Mechanism ◽  
Bladder Function ◽  
Drug Candidate ◽  
Specific Gene ◽  
Muscle Gene Expression ◽  
Muscle Gene

The activity-dependent neuroprotective protein (ADNP), a double-edged sword, sex-dependently regulates multiple genes and was previously associated with the control of early muscle development and aging. Here we aimed to decipher the involvement of ADNP in versatile muscle gene expression patterns in correlation with motor function throughout life. Using quantitative RT-PCR we showed that Adnp+/− heterozygous deficiency in mice resulted in aberrant gastrocnemius (GC) muscle, tongue and bladder gene expression, which was corrected by the Adnp snippet, drug candidate, NAP (CP201). A significant sexual dichotomy was discovered, coupled to muscle and age-specific gene regulation. As such, Adnp was shown to regulate myosin light chain (Myl) in the gastrocnemius (GC) muscle, the language acquisition gene forkhead box protein P2 (Foxp2) in the tongue and the pituitary-adenylate cyclase activating polypeptide (PACAP) receptor PAC1 mRNA (Adcyap1r1) in the bladder, with PACAP linked to bladder function. A tight age regulation was observed, coupled to an extensive correlation to muscle function (gait analysis), placing ADNP as a muscle-regulating gene/protein.

Dynamics of Genomic Organization.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. SCI-17-SCI-17
Author(s):  
Mark T. Groudine ◽  
Indika Rajapakse ◽  
David Scalzo ◽  
Michael Perlman ◽  
Charles L. Kooperberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Genomic Organization ◽  
Conflicts Of Interest ◽  
Cell Types ◽  
Specific Gene ◽  
Chromosomal Association ◽  
Regulated Gene Expression ◽  
Lineage Specific Gene ◽  
Ordered State

Abstract Abstract SCI-17 We have investigated the relationships between lineage-specific gene expression, and total genomic organization during hematopoiesis. First, we determined the linear chromosomal distribution of genes that are co-regulated (identified via microarray analysis) when murine hematopoietic progenitor cells (FDCP-mixA) are differentiated to the erythroid and neutrophil lineages, as well as the organization of all chromosomes (in the form of rosettes) in the three cell types. Our analysis revealed a significant tendency for co-regulated genes to be proximal, which is related to the association of homologous chromosomes and the spatial juxtaposition of lineage-specific gene domains. This led us to hypothesize that the genome—at the level of chromosomes—may self-organize to facilitate coordinate gene regulation during cellular differentiation. We tested this hypothesis by applying the approaches of distance matrices and coupled oscillators to our datasets of gene expression and chromosomal associations from the differentiation of the progenitor to the erythroid and neutrophil lineages. Our analysis revealed that coordinate gene expression undergoes a phase transition—characterized by an increase in entropy—upon commitment of the progenitor. As differentiation continues, there is a gradual loss of entropy, culminating in a highly ordered state in the differentiated cell types. The coregulated gene sets of the semi-ordered progenitor and ordered erythroid and neutrophil lineages are significantly correlated with lineage-specific chromosomal association patterns. Furthermore, by transforming the gene expression networks along the time course to corresponding chromosomal association matrices, we found that chromosomal topologies change dynamically during differentiation but, as with gene expression, result in a more highly ordered state in the differentiated cell types. Our analysis demonstrates that the networks of co-regulated gene expression and chromosomal association are mutually related during differentiation, resulting in the self-organization of lineage-specific chromosomal topologies. Disclosures No relevant conflicts of interest to declare.

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.

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.

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.

A fourth human MEF2 transcription factor, hMEF2D, is an early marker of the myogenic lineage

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1095-1106 ◽  
Author(s):  
R.E. Breitbart ◽  
C.S. Liang ◽  
L.B. Smoot ◽  
D.A. Laheru ◽  
V. Mahdavi ◽  
...  
Keyword(s):  
Myogenic Differentiation ◽  
Specific Binding ◽  
Single Gene ◽  
Cell Types ◽  
Related Factor ◽  
Muscle Gene Expression ◽  
Molecular Events ◽  
Myogenic Lineage ◽  
Muscle Genes ◽  
Muscle Gene

The transition from multipotent mesodermal precursor to committed myoblast and its differentiation into a mature myocyte involve molecular events that enable the cell to activate muscle-specific genes. Among the participants in this process is the myocyte-specific enhancer factor 2 (MEF2) family of tissue-restricted transcription factors. These factors, which share a highly conserved DNA-binding domain including a MADS box, are essential for the expression of multiple muscle genes with cognate target MEF2 sites in cis. We report here a new human MEF2 factor, hMEF2D, which is unique among the members of this family in that it is present not only in myotubes but also in undifferentiated myoblasts, even before the appearance of myogenin. hMEF2D comprises several alternatively spliced products of a single gene, one of which is the human homolog of the Xenopus SRF-related factor SL-1. Like its relatives, cloned hMEF2D is capable of activating transcription via sequence-specific binding to the MEF2 site, recapitulating endogenous tissue-specific MEF2 activity. Indeed, while MEF2D mRNAs are ubiquitous, the protein is highly restricted to those cell types that contain this activity, implicating posttranscriptional mechanisms in the regulation of MEF2D expression. Alternative splicing may be important in this process: two alternative MEF2D domains, at least one of which is specifically included during myogenic differentiation, also correlate precisely with endogenous MEF2 activity. These findings provide compelling evidence that MEF2D is an integral link in the regulatory network for muscle gene expression. Its presence in undifferentiated myoblasts further suggests that it may be a mediator of commitment in the myogenic lineage.

scholarly journals microRNA-1 regulates sarcomere formation and suppresses smooth muscle gene expression in the mammalian heart

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Amy Heidersbach ◽  
Chris Saxby ◽  
Karen Carver-Moore ◽  
Yu Huang ◽  
Yen-Sin Ang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Striated Muscle ◽  
Muscle Gene Expression ◽  
Regulatory Myosin Light Chain ◽  
Myosin Light Chain 2 ◽  
Evolutionarily Conserved ◽  
Muscle Genes ◽  
Mammalian Genomes ◽  
Muscle Gene

microRNA-1 (miR-1) is an evolutionarily conserved, striated muscle-enriched miRNA. Most mammalian genomes contain two copies of miR-1, and in mice, deletion of a single locus, miR-1-2, causes incompletely penetrant lethality and subtle cardiac defects. Here, we report that deletion of miR-1-1 resulted in a phenotype similar to that of the miR-1-2 mutant. Compound miR-1 knockout mice died uniformly before weaning due to severe cardiac dysfunction. miR-1-null cardiomyocytes had abnormal sarcomere organization and decreased phosphorylation of the regulatory myosin light chain-2 (MLC2), a critical cytoskeletal regulator. The smooth muscle-restricted inhibitor of MLC2 phosphorylation, Telokin, was ectopically expressed in the myocardium, along with other smooth muscle genes. miR-1 repressed Telokin expression through direct targeting and by repressing its transcriptional regulator, Myocardin. Our results reveal that miR-1 is required for postnatal cardiac function and reinforces the striated muscle phenotype by regulating both transcriptional and effector nodes of the smooth muscle gene expression network.

scholarly journals Identification of a Novel Slow-Muscle-Fiber Enhancer Binding Protein, MusTRD1

1998 ◽  
Vol 18 (11) ◽  
pp. 6641-6652 ◽  
Author(s):  
John V. O’Mahoney ◽  
Kim L. Guven ◽  
Jia Lin ◽  
Josephine E. Joya ◽  
C. Stephen Robinson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Binding Protein ◽  
Consensus Sequence ◽  
Specific Gene ◽  
Fiber Types ◽  
Muscle Gene Expression ◽  
Slow Fiber ◽  
Muscle Gene ◽  
Bhlh Proteins

ABSTRACT The molecular mechanisms which are responsible for restricting skeletal muscle gene expression to specific fiber types, either slow or fast twitch, are unknown. As a first step toward defining the components which direct slow-fiber-specific gene expression, we identified the sequence elements of the human troponin I slow upstream enhancer (USE) that bind muscle nuclear proteins. These include an E-box, a MEF2 element, and two other elements, USE B1 and USE C1. In vivo analysis of a mutation that disrupts USE B1 binding activity suggested that the USE B1 element is essential for high-level expression in slow-twitch muscles. This mutation does not, however, abolish slow-fiber specificity. A similar analysis indicated that the USE C1 element may play only a minor role. We report the cloning of a novel human USE B1 binding protein, MusTRD1 (muscle TFII-I repeat domain-containing protein 1), which is expressed predominantly in skeletal muscle. Significantly, MusTRD1 contains two repeat domains which show remarkable homology to the six repeat domains of the recently cloned transcription factor TFII-I. Furthermore, both TFII-I and MusTRD1 bind to similar but distinct sequences, which happen to conform with the initiator (Inr) consensus sequence. Given the roles of MEF2 and basic helix-loop-helix (bHLH) proteins in muscle gene expression, the similarity of TFII-I and MusTRD1 is intriguing, as TFII-I is believed to coordinate the interaction of MADS-box proteins, bHLH proteins, and the general transcription machinery.

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