A fast fiber enhancer exists in the muscle regulatory factor 4 gene promoter.
The development of skeletal muscle is a highly regulated process governed by the four myogenic regulatory factors (MRFs) MyoD, myf-5, myogenin, and MRF4. While these factors exhibit some unique functions, part of their individual activity can be attributed to different temporal and spatial expression patterns. To delineate the factors that control expression of the MRFs, we have begun a molecular dissection of the MRF4 gene promoter. Through the generation of promoter/reporter gene constructs, we show that an 853bp fragment, residing 4kb upstream of the MRF4 transcriptional start site (853AV), is able to enhance expression of the basal MRF4 promoter 3-4-fold in myogenic cell cultures. Analysis of the 853AV enhancer in transgenic mice indicates that this region drives MRF4 gene expression primarily in fast muscle fibers, suggesting that the normal adult MRF4 expression pattern is regulated by a variety of control elements that may dictate fiber-type specificity.
Pin
Christopher L
CL
Department of Paediatrics, Child Health Research Institute, University of Western Ontario, Ont., N6C 2V5, London, Canada.
Konieczny
Stephen F
SF
D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured; D002642:Chick Embryo; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000378:metabolism; D017930:Genes, Reporter; D007150:Immunohistochemistry; D007763:Lac Operon; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D018656:Muscle Fibers, Fast-Twitch / Q000473:pathology; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D009132:Muscles / Q000166:cytology*; D017570:MyoD Protein / Q000096:biosynthesis / Q000235:genetics; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors / Q000235:genetics* / Q000378:metabolism*; D018008:Myogenin / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D013997:Time Factors; D014018:Tissue Distribution; D015534:Trans-Activators; D014162:Transfection
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D015534:Trans-Activators; C063403:myogenic factor 6