scholarly journals Direct Interaction between Myocyte Enhancer Factor 2 (MEF2) and Protein Phosphatase 1α Represses MEF2-Dependent Gene Expression

2009 ◽  
Vol 29 (12) ◽  
pp. 3355-3366 ◽  
Author(s):  
R. L. S. Perry ◽  
C. Yang ◽  
N. Soora ◽  
J. Salma ◽  
M. Marback ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Protein Interactions ◽  
Protein Phosphatase ◽  
Hippocampal Neurons ◽  
Neuronal Cell ◽  
Direct Interaction ◽  
Myocyte Enhancer Factor 2 ◽  
Myocyte Enhancer Factor ◽  
Enhancer Factor

ABSTRACT The myocyte enhancer factor 2 (MEF2) transcription factors play important roles in neuronal, cardiac, and skeletal muscle tissues. MEF2 serves as a nuclear sensor, integrating signals from several signaling cascades through protein-protein interactions with kinases, chromatin remodeling factors, and other transcriptional regulators. Here, we report a novel interaction between the catalytic subunit of protein phosphatase 1α (PP1α) and MEF2. Interaction occurs within the nucleus, and binding of PP1α to MEF2 potently represses MEF2-dependent transcription. The interaction utilizes uncharacterized domains in both PP1α and MEF2, and PP1α phosphatase activity is not obligatory for MEF2 repression. Moreover, a MEF2-PP1α regulatory complex leads to nuclear retention and recruitment of histone deacetylase 4 to MEF2 transcription complexes. PP1α-mediated repression of MEF2 overrides the positive influence of calcineurin signaling, suggesting PP1α exerts a dominant level of control over MEF2 function. Indeed, PP1α-mediated repression of MEF2 function interferes with the prosurvival effect of MEF2 in primary hippocampal neurons. The PP1α-MEF2 interaction constitutes a potent locus of control for MEF2-dependent gene expression, having potentially important implications for neuronal cell survival, cardiac remodeling in disease, and terminal differentiation of vascular, cardiac, and skeletal muscle.

scholarly journals Molecular cloning of up-regulated cytoskeletal genes from regenerating skeletal muscle: potential role of myocyte enhancer factor 2 proteins in the activation of muscle-regeneration-associated genes

1997 ◽  
Vol 325 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Waleed M. AKKILA ◽  
Rebecca L. CHAMBERS ◽  
Olga I. ORNATSKY ◽  
John C. McDERMOTT
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Regulatory Protein ◽  
Cdna Clones ◽  
Myocyte Enhancer Factor 2 ◽  
Consensus Binding Site ◽  
Mobility Shift ◽  
Adult Skeletal Muscle ◽  
Myocyte Enhancer Factor ◽  
Enhancer Factor

A subtractive hybridization and cloning strategy was used to identify genes that are up-regulated in regenerating compared with normal skeletal muscle. The gastrocnemius muscle of CD1 mice was injected with a myotoxic agent (BaCl2). A cDNA library was constructed from the regenerating muscle, and was screened with subtracted probes enriched in genes up-regulated during regeneration. Cofilin and vimentin cDNA clones were isolated. Both cofilin and vimentin were demonstrated to be overexpressed in regenerating compared with non-regenerating muscle (17-fold and 19-fold induction respectively). Cofilin and vimentin mRNAs also exhibited an increased expression in C2C12 myoblasts and a decreased expression in differentiated myotubes. Analysis of the regeneration-induced vimentin enhancer/promoter region revealed a consensus binding site for the myocyte enhancer factor 2 (MEF2) transcription factors. Electrophoretic mobility-shift assays and in vivo reporter assays revealed that MEF2 DNA-binding activity and transcriptional activation are increased in regenerating skeletal muscle, indicating that they may play a role in the activation of muscle genes during regeneration. These data suggest that both cofilin (an actin-regulatory protein) and vimentin (an intermediate filament) may be key components of the cytoskeletal reorganization that mediates muscle cell development and adult skeletal-muscle repair.

scholarly journals Direct Interaction of Ca2+/Calmodulin Inhibits Histone Deacetylase 5 Repressor Core Binding to Myocyte Enhancer Factor 2

2003 ◽  
Vol 278 (20) ◽  
pp. 17625-17635 ◽  
Author(s):  
Imre Berger ◽  
Christoph Bieniossek ◽  
Christiane Schaffitzel ◽  
Markus Hassler ◽  
Eugenio Santelli ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Direct Interaction ◽  
Myocyte Enhancer Factor 2 ◽  
Myocyte Enhancer Factor ◽  
Enhancer Factor

Invited Review: Regulation of skeletal muscle GLUT-4 expression by exercise

2002 ◽  
Vol 93 (2) ◽  
pp. 782-787 ◽  
Author(s):  
G. Lynis Dohm
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Control ◽  
Therapeutic Strategies ◽  
Glucose Disposal ◽  
Research Needs ◽  
Maximal Rate ◽  
Myocyte Enhancer Factor 2 ◽  
Glut 4 ◽  
Myocyte Enhancer Factor ◽  
Enhancer Factor

The amount of GLUT-4 protein is a primary factor in determining the maximal rate of glucose transport into skeletal muscle. Therefore, it is important that we understand how exercise regulates GLUT-4 expression so that therapeutic strategies can be designed to increase muscle glucose disposal as a treatment for diabetes. Muscle contraction increases the rates of GLUT-4 transcription and translation. Transcriptional control likely requires at least two DNA binding proteins, myocyte enhancer factor-2 and GLUT-4 enhancer factor, which bind to the promoter. Increased GLUT-4 expression may be mediated by the enzyme AMP-activated kinase, which is activated during exercise and has been demonstrated to increase GLUT-4 transcription. Further research needs to be done to investigate whether AMP-activated kinase activates myocyte enhancer factor-2 and GLUT-4 enhancer factor to increase transcription of the GLUT-4 gene.

scholarly journals Myocyte Enhancer Factor 2 and Chorion Factor 2 Collaborate in Activation of the Myogenic Program in Drosophila

2007 ◽  
Vol 28 (5) ◽  
pp. 1616-1629 ◽  
Author(s):  
Kathleen K. Kelly Tanaka ◽  
Anton L. Bryantsev ◽  
Richard M. Cripps
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Control Cell ◽  
Actin Gene ◽  
Myocyte Enhancer Factor 2 ◽  
Myocyte Enhancer Factor ◽  
General Importance ◽  
Myogenic Program ◽  
Enhancer Factor

ABSTRACT The process of myogenesis requires the coordinated activation of many structural genes whose products are required for myofibril assembly, function, and regulation. Although numerous reports have documented the importance of the myogenic regulator myocyte enhancer factor 2 (MEF2) in muscle differentiation, the interaction of MEF2 with cofactors is critical to the realization of muscle fate. We identify here a genomic region required for full MEF2-mediated activation of actin gene expression in Drosophila, and we identify the zinc finger transcriptional regulator chorion factor 2 (CF2) as a factor functioning alongside MEF2 via this region. Furthermore, although both MEF2 and CF2 can individually activate actin gene expression, we demonstrate that these two factors collaborate in regulating the Actin57B target gene in vitro and in vivo. More globally, MEF2 and CF2 synergistically activate the enhancers of a number of muscle-specific genes, and loss of CF2 function in vivo results in reductions in the levels of several muscle structural gene transcripts. These findings validate a general importance of CF2 alongside MEF2 as a critical regulator of the myogenic program, identify a new regulator functioning with MEF2 to control cell fate, and provide insight into the network of regulatory events that shape the developing musculature.

scholarly journals MEF2 (Myocyte Enhancer Factor 2) Is Essential for Endothelial Homeostasis and the Atheroprotective Gene Expression Program

2021 ◽  
Author(s):  
Yao Wei Lu ◽  
Nina Martino ◽  
Brennan D. Gerlach ◽  
John M. Lamar ◽  
Peter A. Vincent ◽  
...  
Keyword(s):  
Gene Expression ◽  
Shear Stress ◽  
Transcription Factors ◽  
Gene Expression Program ◽  
Binding Motif ◽  
Myocyte Enhancer Factor 2 ◽  
Myocyte Enhancer Factor ◽  
Anti Inflammatory ◽  
Expression Program ◽  
Enhancer Factor

Objective: Atherosclerosis predominantly forms in regions of oscillatory shear stress while regions of laminar shear stress are protected. This protection is partly through the endothelium in laminar flow regions expressing an anti-inflammatory and antithrombotic gene expression program. Several molecular pathways transmitting these distinct flow patterns to the endothelium have been defined. Our objective is to define the role of the MEF2 (myocyte enhancer factor 2) family of transcription factors in promoting an atheroprotective endothelium. Approach and Results: Here, we show through endothelial-specific deletion of the 3 MEF2 factors in the endothelium, Mef2a, -c, and -d, that MEF2 is a critical regulator of vascular homeostasis. MEF2 deficiency results in systemic inflammation, hemorrhage, thrombocytopenia, leukocytosis, and rapid lethality. Transcriptome analysis reveals that MEF2 is required for normal regulation of 3 pathways implicated in determining the flow responsiveness of the endothelium. Specifically, MEF2 is required for expression of Klf2 and Klf4, 2 partially redundant factors essential for promoting an anti-inflammatory and antithrombotic endothelium. This critical requirement results in phenotypic similarities between endothelial-specific deletions of Mef2a/c/d and Klf2/4. In addition, MEF2 regulates the expression of Notch family genes, Notch1, Dll1, and Jag1, which also promote an atheroprotective endothelium. In contrast to these atheroprotective pathways, MEF2 deficiency upregulates an atherosclerosis promoting pathway through increasing the amount of TAZ (transcriptional coactivator with PDZ-binding motif). Conclusions: Our results implicate MEF2 as a critical upstream regulator of several transcription factors responsible for gene expression programs that affect development of atherosclerosis and promote an anti-inflammatory and antithrombotic endothelium.

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