scholarly journals A new serum-responsive, cardiac tissue-specific transcription factor that recognizes the MEF-2 site in the myosin light chain-2 promoter.

1993 ◽  
Vol 13 (2) ◽  
pp. 1222-1231 ◽  
Author(s):  
M D Zhou ◽  
S K Goswami ◽  
M E Martin ◽  
M A Siddiqui
Keyword(s):  
Transcription Factor ◽  
Cardiac Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Cardiac Tissue ◽  
Muscle Cells ◽  
Cardiac Muscle Cells ◽  
Tissue Specific ◽  
Specific Transcription Factor ◽  
Myosin Light Chain 2

We have identified a serum-responsive, cardiac tissue-specific transcription factor, BBF-1, that recognizes an AT-rich sequence (element B), identical to the myocyte enhancer factor (MEF-2) target site, in the cardiac myosin light chain-2 (MLC-2) promoter. Deletion of the element B sequence alone from the cardiac MLC-2 promoter causes, as does that of the MEF-2 site from other promoters and the enhancer of skeletal muscle genes, a marked reduction of transcription. BBF-1 is distinguishable from cardiac MEF-2 on the basis of immunoprecipitation with an antibody which recognizes MEF-2 but not BBF-1. Unlike MEF-2, BBF-1 is present exclusively in nuclear extracts from cardiac muscle cells cultured in a medium containing a high concentration of serum. Removal of serum from culture medium abolishes BBF-1 activity selectively with a concomitant loss of the positive regulatory effect of element B on MLC-2 gene transcription, indicating that there is a correlation between the BBF-1 binding activity and the tissue-specific role of the element B (MEF-2 site) sequence. The loss of element B-mediated activation of transcription is reversed following the refeeding of cells with serum-containing medium. These data demonstrate that cardiac muscle cells contain two distinct protein factors, MEF-2 and BBF-1, which bind to the same target site but that, unlike MEF-2, BBF-1 is serum inducible and cardiac tissue specific. BBF-1 thus appears to be a crucial member of the MEF-2 family of proteins which will serve as an important tool in understanding the regulatory mechanism(s) underlying cardiogenic differentiation.

A new serum-responsive, cardiac tissue-specific transcription factor that recognizes the MEF-2 site in the myosin light chain-2 promoter

1993 ◽  
Vol 13 (2) ◽  
pp. 1222-1231
Author(s):  
M D Zhou ◽  
S K Goswami ◽  
M E Martin ◽  
M A Siddiqui
Keyword(s):  
Transcription Factor ◽  
Cardiac Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Cardiac Tissue ◽  
Muscle Cells ◽  
Cardiac Muscle Cells ◽  
Tissue Specific ◽  
Specific Transcription Factor ◽  
Myosin Light Chain 2

We have identified a serum-responsive, cardiac tissue-specific transcription factor, BBF-1, that recognizes an AT-rich sequence (element B), identical to the myocyte enhancer factor (MEF-2) target site, in the cardiac myosin light chain-2 (MLC-2) promoter. Deletion of the element B sequence alone from the cardiac MLC-2 promoter causes, as does that of the MEF-2 site from other promoters and the enhancer of skeletal muscle genes, a marked reduction of transcription. BBF-1 is distinguishable from cardiac MEF-2 on the basis of immunoprecipitation with an antibody which recognizes MEF-2 but not BBF-1. Unlike MEF-2, BBF-1 is present exclusively in nuclear extracts from cardiac muscle cells cultured in a medium containing a high concentration of serum. Removal of serum from culture medium abolishes BBF-1 activity selectively with a concomitant loss of the positive regulatory effect of element B on MLC-2 gene transcription, indicating that there is a correlation between the BBF-1 binding activity and the tissue-specific role of the element B (MEF-2 site) sequence. The loss of element B-mediated activation of transcription is reversed following the refeeding of cells with serum-containing medium. These data demonstrate that cardiac muscle cells contain two distinct protein factors, MEF-2 and BBF-1, which bind to the same target site but that, unlike MEF-2, BBF-1 is serum inducible and cardiac tissue specific. BBF-1 thus appears to be a crucial member of the MEF-2 family of proteins which will serve as an important tool in understanding the regulatory mechanism(s) underlying cardiogenic differentiation.

scholarly journals Tissue-specific transcription of the cardiac myosin light-chain 2 gene is regulated by an upstream repressor element.

1991 ◽  
Vol 11 (3) ◽  
pp. 1676-1685 ◽  
Author(s):  
R A Shen ◽  
S K Goswami ◽  
E Mascareno ◽  
A Kumar ◽  
M A Siddiqui
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Cardiac Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Tissue Specific ◽  
Myosin Light Chain 2 ◽  
Functional Components

Physiological expression of the cardiac muscle myosin light-chain 2 (MLC-2) gene in chickens is restricted to cardiac muscle tissue only, at least during the late embryonic to adult stages of development. The mechanism by which cardiac MLC-2 gene expression is repressed in differentiated noncardiac muscle tissues is unknown. Using sequential 5'-deletion mutants of the cardiac MLC-2 promoter introduced into primary skeletal muscle cells in culture, we have demonstrated that a 89-bp region, designated the cardiac-specific sequence (CSS), is essential for repression of cardiac MLC-2 expression in skeletal muscle. Removal of the CSS sequence alone allows transcription in skeletal muscle cells without affecting the transcriptional activity of the promoter in cardiac muscle cells. DNase I footprinting and gel shift assays indicate that protein binding to sequences in the CSS domain occurs readily in nuclear extracts obtained from skeletal muscle but not in extracts isolated under identical conditions from cardiac muscle. Thus, it appears that a negative regulatory mechanism accounts for the lack of expression of the cardiac MLC-2 gene in skeletal muscle and that the CSS element and its binding proteins are important functional components of the regulatory apparatus which ensures the developmental program for cardiac tissue-specific gene expression.

Tissue-specific transcription of the cardiac myosin light-chain 2 gene is regulated by an upstream repressor element

1991 ◽  
Vol 11 (3) ◽  
pp. 1676-1685
Author(s):  
R A Shen ◽  
S K Goswami ◽  
E Mascareno ◽  
A Kumar ◽  
M A Siddiqui
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Cardiac Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Tissue Specific ◽  
Myosin Light Chain 2 ◽  
Functional Components

Physiological expression of the cardiac muscle myosin light-chain 2 (MLC-2) gene in chickens is restricted to cardiac muscle tissue only, at least during the late embryonic to adult stages of development. The mechanism by which cardiac MLC-2 gene expression is repressed in differentiated noncardiac muscle tissues is unknown. Using sequential 5'-deletion mutants of the cardiac MLC-2 promoter introduced into primary skeletal muscle cells in culture, we have demonstrated that a 89-bp region, designated the cardiac-specific sequence (CSS), is essential for repression of cardiac MLC-2 expression in skeletal muscle. Removal of the CSS sequence alone allows transcription in skeletal muscle cells without affecting the transcriptional activity of the promoter in cardiac muscle cells. DNase I footprinting and gel shift assays indicate that protein binding to sequences in the CSS domain occurs readily in nuclear extracts obtained from skeletal muscle but not in extracts isolated under identical conditions from cardiac muscle. Thus, it appears that a negative regulatory mechanism accounts for the lack of expression of the cardiac MLC-2 gene in skeletal muscle and that the CSS element and its binding proteins are important functional components of the regulatory apparatus which ensures the developmental program for cardiac tissue-specific gene expression.

scholarly journals A single transcription factor binds to two divergent sequence elements with a common function in cardiac myosin light chain-2 promoter.

1992 ◽  
Vol 12 (3) ◽  
pp. 1107-1116 ◽  
Author(s):  
P Qasba ◽  
E Lin ◽  
M D Zhou ◽  
A Kumar ◽  
M A Siddiqui
Keyword(s):  
Transcription Factor ◽  
Gene Transcription ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Cardiac Myosin ◽  
Divergent Sequence ◽  
Specific Element ◽  
Myosin Light Chain 2 ◽  
Sequence Elements ◽  
Gel Shift

The cardiac myosin light chain-2 (MLC-2) gene promoter contains several positive and negative cis-acting sequences that are involved in the regulation of its expression. We describe here the properties of two activator sequences, elements A and P, and their DNA-binding factors (ABFs). Element A (CCAAAAGTGG), located at -61, has homology with the evolutionarily conserved sequence CC(A/T)6GG, present in the genes of many contractile proteins. Element P (TAACCTTGAAAGC), located 114 bp upstream of element A, is conserved in both chicken and rat cardiac MLC-2 gene promoters. Deletion mutagenesis demonstrated that these two elements are involved in the positive regulation of MLC-2 gene transcription. At least two sequence-specific element A-binding proteins, ABF-1 and ABF-2, were identified by gel shift analysis of the fractionated cardiac nuclear proteins. ABF-1 binds to element A with strict dependence on the internal element A sequence AAAAGT. In contrast, ABF-2 exhibits a relaxed sequence requirement, as it recognizes the consensus CArG and CCAAT box sequences as well. ABF-2 also recognizes the distal element P despite the fact that the sequences of elements A and P are divergent. DNase I footprinting, methylation interference, and gel shift analyses demonstrated unequivocally that the element A-DNA affinity-purified protein ABF-2 binds to element P with sequence specificity. Since both elements A and P play a positive regulatory role in MLC-2 gene transcription and bind to a single protein (ABF-2), it would appear that ABF-2 is a key transcription factor with the ability to recognize divergent sequence elements involved in a common regulatory pathway during myogenesis.

scholarly journals Inhibition of transcription factor GATA-4 expression blocks in vitro cardiac muscle differentiation.

1995 ◽  
Vol 15 (8) ◽  
pp. 4095-4102 ◽  
Author(s):  
C Grépin ◽  
L Robitaille ◽  
T Antakly ◽  
M Nemer
Keyword(s):  
Transcription Factor ◽  
Cardiac Muscle ◽  
Heart Development ◽  
Muscle Cells ◽  
Cardiac Differentiation ◽  
Marker Genes ◽  
Early Event ◽  
Heart Tube ◽  
Cardiac Muscle Cells ◽  
Cardiac Lineage

Commitment of mesodermal cells to the cardiac lineage is a very early event that occurs during gastrulation, and differentiation of cardiac muscle cells begins in the presomite stage prior to formation of the beating heart tube. However, the molecular events, including gene products that are required for differentiation of cardiac muscle cells, remain essentially unknown. GATA-4 is a recently characterized cardiac muscle-restricted transcription factor whose properties suggest an important regulatory role in heart development. We tested the role of GATA-4 in cardiac differentiation, using the pluripotent P19 embryonal carcinoma cells, which can be differentiated into beating cardiac muscle cells. In this system, GATA-4 transcripts and protein are restricted to cells committed to the cardiac lineage, and induction of GATA-4 precedes expression of cardiac marker genes and appearance of beating cells. Inhibition of GATA-4 expression by antisense transcripts blocks development of beating cardiac muscle cells and interferes with expression of cardiac muscle markers. These data indicate that GATA-4 is necessary for development of cardiac muscle cells and identify for the first time a tissue-specific transcription factor that may be crucial for early steps of mammalian cardiogenesis.

scholarly journals Functions of myosin light chain-2 (MYL2) in cardiac muscle and disease

Gene ◽  
2015 ◽  
Vol 569 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Farah Sheikh ◽  
Robert C. Lyon ◽  
Ju Chen
Keyword(s):  
Cardiac Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Myosin Light Chain 2
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