Functionally distinct elements are required for expression of the AMPD1 gene in myocytes.
AMP deaminase (AMPD) is an enzyme found in all eukaryotic cells. Tissue-specific and stage-specific isoforms of this enzyme are found in vertebrates, and expression of these different isoforms is determined by selective expression of the multiple genes. The AMPD1 gene is expressed predominantly in skeletal muscle, in which transcript abundance is controlled by stage-specific and fiber type-specific signals. This enzyme activity is presumed to be important in skeletal muscle because a metabolic myopathy develops in individuals with an inherited deficiency of AMPD1. In the present study, cis- and trans-acting factors that control expression of AMPD1 have been identified. Two cis-acting elements located within 100 nucleotides of the transcriptional start site are required for muscle-specific expression of AMPD1. One element (-100 to -79) behaves like a tissue-specific enhancer, and it interacts with protein(s) found predominantly in nuclei of myoblasts and myotubes. This element is similar in sequence to an MEF2 binding motif, and it contains an A/T core that is essential for enhancer activity and binding of a nuclear protein(s). The second element (-60 to -40) has properties of a stage-specific promoter in that it is essential for muscle-specific expression of the AMPD1 promoter, does not confer muscle-specific expression on a heterologous promoter construct, and interacts with a protein(s) restricted to nuclei of differentiated myotubes. Interaction between these functionally distinct elements may be required for regulating the expression of AMPD1 during myocyte differentiation and in different muscle fiber types.
Morisaki
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Seymour Gray Molecular Medicine Laboratory, Department of Medicine and Human Genetics, University of Pennsylvania, Philadelphia 19104-4283.
Holmes
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D016475:3T3 Cells; D000659:AMP Deaminase / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D009132:Muscles / Q000166:cytology / Q000201:enzymology*; D011401:Promoter Regions, Genetic; D051381:Rats; D016415:Sequence Alignment; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013329:Structure-Activity Relationship
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D016329:Sp1 Transcription Factor; D000659:AMP Deaminase