The A17 enhancer directs expression of Myf5 to muscle satellite cells but Mrf4 to myonuclei.
The myogenic regulatory factors, Myf5 and Mrf4, play key roles in the specification and differentiation of skeletal muscle, respectively. Many cis-acting regulatory elements at the Mrf4/Myf5 locus have been identified, including the A17 enhancer. During development, A17 in conjunction with the Mrf4 or Myf5 promoter, directs transgene expression either to embryonic or fetal muscles. We now show that this enhancer also regulates Mrf4/Myf5 transcription in the adult. A17 linked to the Myf5 promoter drives expression in muscle satellite cells, whereas with the Mrf4 promoter, A17 directs transgene expression to myonuclei. Interestingly, expression of A17-Mrf4-nlacZ transgenes in myonuclei varies between muscles, revealing muscle autonomous transcriptional regulation. During muscle repair, satellite cells are induced to proliferate and differentiate to provide new myonuclei. A17 directs Myf5 expression in satellite cell progeny while it only drives the Mrf4 promoter after differentiation. Importantly, therefore, this promoter-specific activity directed by A17 reflects aspects of the expression profiles of the endogenous Myf5 and Mrf4 genes.
Chang
Ted Hung-Tse
TH
Département de Biologie du Développement, CNRS URA 2578, Institut Pasteur, Paris, France.
Vincent
Stéphane D
SD
Buckingham
Margaret E
ME
Zammit
Peter S
PS
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004742:Enhancer Elements, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics* / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism*
C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; C063403:myogenic factor 6