Positive autoregulation of the Myocyte enhancer factor-2 myogenic control gene during somatic muscle development in Drosophila.
The myocyte enhancer factor-2 (MEF2) transcription factor plays a central role in the activation and maintenance of muscle gene expression in fruit flies and vertebrates. The mechanism of action and downstream target genes of MEF2 have been defined in considerable detail, but relatively little is known about the mechanisms that regulate MEF2 expression during muscle development. Here we demonstrate that MEF2 maintains its own expression in all differentiated muscle cell types during late embryonic and larval development in Drosophila by binding a conserved MEF2 site in a muscle-specific regulatory enhancer. Ectopic expression of Mef2 is sufficient to directly activate this enhancer in some, but not all, non-muscle cells. Furthermore, activation of the Mef2 enhancer normally in muscle cells and ectopically in non-muscle cells is dependent upon the integrity of the MEF2 binding site. These findings suggest an evolutionarily conserved mechanism whereby MEF2 can stabilize the muscle phenotype by sustaining its own expression through a myogenic autoregulatory loop.
Cripps
Richard M
RM
Department of Biology, University of New Mexico, Albuquerque, NM 87131-1091, USA. rcripps@unm.edu
Lovato
TyAnna L
TL
Olson
Eric N
EN
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D003433:Crosses, Genetic; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics; D007150:Immunohistochemistry; D007814:Larva / Q000254:growth & development; D064326:MEF2 Transcription Factors; D024510:Muscle Development; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D064326:MEF2 Transcription Factors; C499409:Mef2 protein, Drosophila; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors