Myocardin Is a Master Regulator of Smooth Muscle Gene Expression

Virtually all smooth muscle genes analyzed to date contain two or more essential binding sites for serum response factor (SRF) in their control regions. Because SRF is expressed in a wide range of cell types, it alone cannot account for smooth muscle-specific gene expression. We show that myocardin,...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2003-06, Vol.100 (12), p.7129-7134
Main Authors: Wang, Zhigao, Wang, Da-Zhi, G. C. Teg Pipes, Olson, Eric N.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antibodies
Binding Sites - genetics
Biological Sciences
Biology
Cell Line
Cell lines
Cells, Cultured
COS cells
Dimerization
Gene expression
Gene Expression Regulation, Developmental
Genes
Mice
Models, Biological
Molecular Sequence Data
Molecular Structure
Muscle, Smooth - growth & development
Muscle, Smooth - metabolism
Muscular system
Mutation
Myocardium
Myocardium - metabolism
Nuclear Proteins - chemistry
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Rats
Reverse transcriptase polymerase chain reaction
Serum Response Factor - metabolism
Skeletal muscle
Smooth muscle
Trans-Activators - chemistry
Trans-Activators - genetics
Trans-Activators - metabolism
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Summary:Virtually all smooth muscle genes analyzed to date contain two or more essential binding sites for serum response factor (SRF) in their control regions. Because SRF is expressed in a wide range of cell types, it alone cannot account for smooth muscle-specific gene expression. We show that myocardin, a cardiac muscle- and smooth muscle-specific transcriptional coactivator of SRF, can activate smooth muscle gene expression in a variety of nonmuscle cell types via its association with SRF. Homodimerization of myocardin is required for maximal transcriptional activity and provides a mechanism for cooperative activation of smooth muscle genes by SRF-myocardin complexes bound to different SRF binding sites. These findings identify myocardin as a master regulator of smooth muscle gene expression and explain how SRF conveys smooth muscle specificity to its target genes.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1232341100