scholarly journals Different regulatory sequences control creatine kinase-M gene expression in directly injected skeletal and cardiac muscle.

1993 ◽  
Vol 13 (2) ◽  
pp. 1264-1272 ◽  
Author(s):  
C K Vincent ◽  
A Gualberto ◽  
C V Patel ◽  
K Walsh
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Cardiac Muscle ◽  
Serum Response Factor ◽  
Sequence Motif ◽  
Regulatory Sequences ◽  
Response Factor ◽  
Specific Expression ◽  
Serum Response

Regulatory sequences of the M isozyme of the creatine kinase (MCK) gene have been extensively mapped in skeletal muscle, but little is known about the sequences that control cardiac-specific expression. The promoter and enhancer sequences required for MCK gene expression were assayed by the direct injection of plasmid DNA constructs into adult rat cardiac and skeletal muscle. A 700-nucleotide fragment containing the enhancer and promoter of the rabbit MCK gene activated the expression of a downstream reporter gene in both muscle tissues. Deletion of the enhancer significantly decreased expression in skeletal muscle but had no detectable effect on expression in cardiac muscle. Further deletions revealed a CArG sequence motif at position -179 within the promoter that was essential for cardiac-specific expression. The CArG element of the MCK promoter bound to the recombinant serum response factor and YY1, transcription factors which control expression from structurally similar elements in the skeletal actin and c-fos promoters. MCK-CArG-binding activities that were similar or identical to serum response factor and YY1 were also detected in extracts from adult cardiac muscle. These data suggest that the MCK gene is controlled by different regulatory programs in adult cardiac and skeletal muscle.

scholarly journals Different regulatory sequences control creatine kinase-M gene expression in directly injected skeletal and cardiac muscle

1993 ◽  
Vol 13 (2) ◽  
pp. 1264-1272
Author(s):  
C K Vincent ◽  
A Gualberto ◽  
C V Patel ◽  
K Walsh
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Cardiac Muscle ◽  
Serum Response Factor ◽  
Sequence Motif ◽  
Regulatory Sequences ◽  
Response Factor ◽  
Specific Expression ◽  
Serum Response

Regulatory sequences of the M isozyme of the creatine kinase (MCK) gene have been extensively mapped in skeletal muscle, but little is known about the sequences that control cardiac-specific expression. The promoter and enhancer sequences required for MCK gene expression were assayed by the direct injection of plasmid DNA constructs into adult rat cardiac and skeletal muscle. A 700-nucleotide fragment containing the enhancer and promoter of the rabbit MCK gene activated the expression of a downstream reporter gene in both muscle tissues. Deletion of the enhancer significantly decreased expression in skeletal muscle but had no detectable effect on expression in cardiac muscle. Further deletions revealed a CArG sequence motif at position -179 within the promoter that was essential for cardiac-specific expression. The CArG element of the MCK promoter bound to the recombinant serum response factor and YY1, transcription factors which control expression from structurally similar elements in the skeletal actin and c-fos promoters. MCK-CArG-binding activities that were similar or identical to serum response factor and YY1 were also detected in extracts from adult cardiac muscle. These data suggest that the MCK gene is controlled by different regulatory programs in adult cardiac and skeletal muscle.

scholarly journals New Role for Serum Response Factor in Postnatal Skeletal Muscle Growth and Regeneration via the Interleukin 4 and Insulin-Like Growth Factor 1 Pathways

2006 ◽  
Vol 26 (17) ◽  
pp. 6664-6674 ◽  
Author(s):  
Claude Charvet ◽  
Christophe Houbron ◽  
Ara Parlakian ◽  
Julien Giordani ◽  
Charlotte Lahoute ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Serum Response Factor ◽  
Muscle Growth ◽  
Interleukin 4 ◽  
Specific Gene ◽  
Response Factor ◽  
Insulin Like Growth Factor ◽  
Serum Response

ABSTRACT Serum response factor (SRF) is a crucial transcriptional factor for muscle-specific gene expression. We investigated SRF function in adult skeletal muscles, using mice with a postmitotic myofiber-targeted disruption of the SRF gene. Mutant mice displayed severe skeletal muscle mass reductions due to a postnatal muscle growth defect resulting in highly hypotrophic adult myofibers. SRF-depleted myofibers also failed to regenerate following injury. Muscles lacking SRF had very low levels of muscle creatine kinase and skeletal alpha-actin (SKA) transcripts and displayed other alterations to the gene expression program, indicating an overall immaturity of mutant muscles. This loss of SKA expression, together with a decrease in beta-tropomyosin expression, contributed to myofiber growth defects, as suggested by the extensive sarcomere disorganization found in mutant muscles. However, we observed a downregulation of interleukin 4 (IL-4) and insulin-like growth factor 1 (IGF-1) expression in mutant myofibers which could also account for their defective growth and regeneration. Indeed, our demonstration of SRF binding to interleukin 4 and IGF-1 promoters in vivo suggests a new crucial role for SRF in pathways involved in muscle growth and regeneration.

The single-strand DNA/RNA-binding protein, Purβ, regulates serum response factor (SRF)-mediated cardiac muscle gene expressionThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.

2007 ◽  
Vol 85 (3-4) ◽  
pp. 349-359 ◽  
Author(s):  
Madhu Gupta ◽  
Vithida Sueblinvong ◽  
Mahesh P. Gupta
Keyword(s):  
Gene Expression ◽  
Cardiac Muscle ◽  
Rna Binding ◽  
Serum Response Factor ◽  
Single Strand ◽  
Specific Gene ◽  
Response Factor ◽  
Repressive Effect ◽  
Muscle Gene ◽  
Serum Response

Single-strand DNA-binding proteins, Purα and Purβ, play a role in cell growth and differentiation by modulating both transcriptional and translational controls of gene expression. We have previously characterized binding of Purα and Purβ proteins to a purine-rich negative regulatory (PNR) element of the rat cardiac α-myosin heavy chain (MHC) gene that controls cardiac muscle specificity. In this study we investigated the role of upstream sequences of the α-MHC promoter in Purβ-mediated gene repression. In the transient transfection analysis overexpression of Purβ revealed a negative regulatory effect on serum response factor (SRF)-dependent α-MHC and α-skeletal actin expression in muscle cell background. Contrary, in nonmuscle cells, Purβ showed no repressive effect. The results obtained from gel-shift assays demonstrated a sequence specific competitive binding of Purβ to the minus strand of the SRF-binding, CArG box sequences of different muscle genes, but not to the SRF-binding, SRE sequences of the c-fos gene. These element-specific associations of Purβ with muscle CArG boxes may, in part, explain why muscle gene expression is downregulated in disease states in which Purβ levels are elevated. This data also provide a mechanistic distinction between muscle CArG boxes and nonmuscle serum response element (SRE) sequences in terms of their affinity to bind to SRF and their ability to regulate cell-specific gene expression.

Cardiomyopathy in transgenic mice with cardiac-specific overexpression of serum response factor

2001 ◽  
Vol 280 (4) ◽  
pp. H1782-H1792 ◽  
Author(s):  
Xiaomin Zhang ◽  
Gohar Azhar ◽  
Jianyuan Chai ◽  
Pamela Sheridan ◽  
Koichiro Nagano ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cardiac Muscle ◽  
Serum Response Factor ◽  
Interstitial Fibrosis ◽  
Weight Ratio ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Response Factor ◽  
Serum Response

Serum response factor (SRF), a member of the MCM1, agamous, deficiens, SRF (MADS) family of transcriptional activators, has been implicated in the transcriptional control of a number of cardiac muscle genes, including cardiac α-actin, skeletal α-actin, α-myosin heavy chain (α-MHC), and β-MHC. To better understand the in vivo role of SRF in regulating genes responsible for maintenance of cardiac function, we sought to test the hypothesis that increased cardiac-specific SRF expression might be associated with altered cardiac morphology and function. We generated transgenic mice with cardiac-specific overexpression of the human SRF gene. The transgenic mice developed cardiomyopathy and exhibited increased heart weight-to-body weight ratio, increased heart weight, and four-chamber dilation. Histological examination revealed cardiomyocyte hypertrophy, collagen deposition, and interstitial fibrosis. SRF overexpression altered the expression of SRF-regulated genes and resulted in cardiac muscle dysfunction. Our results demonstrate that sustained overexpression of SRF, in the absence of other stimuli, is sufficient to induce cardiac change and suggest that SRF is likely to be one of the downstream effectors of the signaling pathways involved in mediating cardiac hypertrophy.

Telokin expression in A10 smooth muscle cells requires serum response factor

1997 ◽  
Vol 272 (4) ◽  
pp. C1394-C1404 ◽  
Author(s):  
B. P. Herring ◽  
A. F. Smith
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Transcription Initiation ◽  
Serum Response Factor ◽  
Muscle Cells ◽  
Tata Box ◽  
Luciferase Reporter ◽  
Response Factor ◽  
Specific Expression ◽  
Serum Response

Telokin transcription is initiated from a smooth muscle-specific promoter located in an intron of the smooth muscle myosin light chain kinase gene. We have previously identified a 310-base pair fragment of the promoter that mediates A10 smooth muscle cell-specific expression of telokin. In the current study, telokin-luciferase reporter gene assays in A10 cells and REF52 nonmuscle cells revealed that the promoter region between -81 and +80 contains the regulatory elements required to mediate the in vitro cell specificity of the promoter. Several positive-acting elements, including an E box, myocyte enhancer factor 2 (MEF2)-TATA box, and CArG-serum response element, were identified within this region. Telokin transcription in A10 smooth muscle cells requires all three transcription initiation sites and an AT-rich sequence between -71 and -62 that includes a TATA box. MEF2 interacts with the AT-rich region with low affinity; however, MEF2 binding is not required for transcriptional activity in A10 cells. Binding of serum response factor (SRF) to a CArG element proximal to the TATA sequence is also critical for high levels of transcription in A10 cells. Together these data suggest that an AT-rich motif, acting in concert with SRF and an unusual transcription initiation mechanism, is required for the cell-specific expression of the telokin promoter in A10 smooth muscle cells.

Alternative splicing and nonsense-mediated mRNA decay regulate gene expression of serum response factor

Gene ◽  
2007 ◽  
Vol 400 (1-2) ◽  
pp. 131-139 ◽  
Author(s):  
Xiaomin Zhang ◽  
Gohar Azhar ◽  
Chris Huang ◽  
Cunqi Cui ◽  
Ying Zhong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Mrna Decay ◽  
Serum Response Factor ◽  
Response Factor ◽  
Regulate Gene Expression ◽  
Nonsense Mediated Mrna Decay ◽  
Serum Response ◽  
Regulate Gene

scholarly journals Serum Response Factor Regulates Immediate Early Host Gene Expression in Toxoplasma gondii-Infected Host Cells

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e18335 ◽  
Author(s):  
Mandi Wiley ◽  
Crystal Teygong ◽  
Eric Phelps ◽  
Jay Radke ◽  
Ira J. Blader
Keyword(s):  
Gene Expression ◽  
Toxoplasma Gondii ◽  
Serum Response Factor ◽  
Host Gene ◽  
Host Cells ◽  
Immediate Early ◽  
Infected Host ◽  
Response Factor ◽  
Host Gene Expression ◽  
Serum Response

scholarly journals OTT-MAL Is a Deregulated Activator of Serum Response Factor-Dependent Gene Expression

2008 ◽  
Vol 28 (20) ◽  
pp. 6171-6181 ◽  
Author(s):  
Arnaud Descot ◽  
Monika Rex-Haffner ◽  
Geneviève Courtois ◽  
Dominique Bluteau ◽  
Antje Menssen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fusion Protein ◽  
Serum Response Factor ◽  
Mitogen Activated Protein Kinase ◽  
Binding Motif ◽  
Fusion Partner ◽  
Response Factor ◽  
Transactivation Domain ◽  
Regulated Gene Expression ◽  
Serum Response

ABSTRACT The OTT-MAL/RBM15-MKL1 fusion protein is the result of the recurrent translocation t(1;22) in acute megakaryocytic leukemia in infants. How it contributes to the malignancy is unknown. The 3′ fusion partner, MAL/MKL1/MRTF-A, is a transcriptional coactivator of serum response factor (SRF). MAL plays a key role in regulated gene expression depending on Rho family GTPases and G-actin. Here we demonstrate that OTT-MAL is a constitutive activator of SRF and target gene expression. This requires the SRF-binding motif and the MAL-derived transactivation domain. OTT-MAL localizes to the nucleus and is not regulated by upstream signaling. OTT-MAL deregulation reflects its independence from control by G-actin, which fails to interact with OTT-MAL in coimmunoprecipitation experiments. Regulation cannot be restored by reintroduction of the entire MAL N terminus into the fusion protein. OTT-MAL also caused a delayed induction of the MAL-independent, ternary complex factor-dependent target genes c-fos and egr-1 and the mitogen-activated protein kinase/Erk pathway. With testing in heterologous tissue culture systems, however, we observed considerable antiproliferative effects of OTT-MAL. Our data suggest that the deregulated activation of MAL-dependent and -independent promoters results in tissue-specific functions of OTT-MAL.

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