Abstract
Expression of the mouse alpha-cardiac actin gene in skeletal and cardiac muscle is regulated by enhancers lying 5' to the proximal promoter. Here we report the characterization of a cardiac-specific enhancer located within -2.354/-1.36 kbp of the gene, which is active in cardiocytes but not in C2 skeletal muscle cells. In vivo it directs reporter gene expression to the adult heart, where the proximal promoter alone is inactive. An 85-bp region within the enhancer is highly conserved between human and mouse and contains a central AT-rich site, which is essential for enhancer activity. This site binds myocyte enhancer factor (MEF)2 factors, principally MEF2D and MEF2A in cardiocyte nuclear extracts. These results are discussed in the context of MEF2 activity and of the regulation of the alpha-cardiac actin locus.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Actins / chemistry*
-
Animals
-
Animals, Genetically Modified
-
Base Sequence
-
Binding Sites
-
Binding, Competitive
-
Cell Line
-
Cell Nucleus / metabolism
-
Cells, Cultured
-
DNA / metabolism
-
DNA-Binding Proteins / metabolism
-
Enhancer Elements, Genetic*
-
Gene Expression Regulation*
-
Gene Expression Regulation, Developmental
-
Genes, Reporter
-
Genome
-
Heart / embryology*
-
Heart / physiology*
-
Humans
-
MADS Domain Proteins
-
MEF2 Transcription Factors
-
Mice
-
Mice, Inbred C3H
-
Mice, Transgenic
-
Models, Genetic
-
Molecular Sequence Data
-
Muscle, Skeletal / metabolism
-
Mutagenesis, Site-Directed
-
Mutation
-
Myocardium / metabolism*
-
Myogenic Regulatory Factors
-
Promoter Regions, Genetic
-
Rats
-
Rats, Wistar
-
Time Factors
-
Transcription Factors / metabolism
-
Transcription, Genetic*
-
Transfection
-
beta-Galactosidase / metabolism
Substances
-
Actins
-
DNA-Binding Proteins
-
MADS Domain Proteins
-
MEF2 Transcription Factors
-
MEF2A protein, human
-
MEF2D protein, human
-
Mef2a protein, mouse
-
Mef2d protein, mouse
-
Myogenic Regulatory Factors
-
Transcription Factors
-
DNA
-
beta-Galactosidase