An enhancer directs differential expression of the linked Mrf4 and Myf5 myogenic regulatory genes in the mouse.
The myogenic regulatory factors, Mrf4 and Myf5, play a key role in skeletal muscle formation. An enhancer trap approach, devised to isolate positive-acting elements from a 200-kb YAC covering the mouse Mrf4-Myf5 locus in a C2 myoblast assay, yielded an enhancer, A17, which mapped at -8 kb 5' of Mrf4 and -17 kb 5' of Myf5. An E-box bound by complexes containing the USF transcription factor is critical for enhancer activity. In transgenic mice, A17 gave two distinct and mutually exclusive expression profiles before birth, which correspond to two phases of Mrf4 transcription. Linked to the Tk or Mrf4 minimal promoters, the nlacZ reporter was expressed either in embryonic myotomes, or later in fetal muscle, with the majority of Mrf4 lines showing embryonic expression. When linked to the Myf5 minimal promoter, only fetal muscle expression was detected. These observations identify A17 as a sequence that targets sites of myogenesis in vivo and raise questions about the mutually exclusive modes of expression and possible promoter/enhancer interactions at the Mrf4-Myf5 locus.
Chang
Ted Hung-Tse
TH
Département de Biologie du Développement, CNRS URA 2578, Institut Pasteur, 75724 Paris Cedex 15, France.
Primig
Michael
M
Hadchouel
Juliette
J
Tajbakhsh
Shahragim
S
Rocancourt
Didier
D
Fernandez
Anne
A
Kappler
Roland
R
Scherthan
Harry
H
Buckingham
Margaret
M
D000818:Animals; D004268:DNA-Binding Proteins; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D005697:Galactosides / Q000032:analysis; D018507:Gene Expression Regulation, Developmental; D007211:Indoles / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D024510:Muscle Development; D009124:Muscle Proteins / Q000235:genetics*; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors / Q000235:genetics*; D011401:Promoter Regions, Genetic; D015534:Trans-Activators
D004268:DNA-Binding Proteins; D005697:Galactosides; D007211:Indoles; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D015534:Trans-Activators; C063403:myogenic factor 6; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside