A combination of MEF3 and NFI proteins activates transcription in a subset of fast-twitch muscles.
The human aldolase A pM promoter is active in fast-twitch muscles. To understand the role of the different transcription factors which bind to this promoter and determine which ones are responsible for its restricted pattern of expression, we analyzed several transgenic lines harboring different combinations of pM regulatory elements. We show that muscle-specific expression can be achieved without any binding sites for the myogenic factors MyoD and MEF2 and that a 64-bp fragment comprising a MEF3 motif and an NFI binding site is sufficient to drive reporter gene expression in some but, interestingly, not all fast-twitch muscles. A result related to this pattern of expression is that some isoforms of NFI proteins accumulate differentially in fast- and slow-twitch muscles and in distinct fast-twitch muscles. We propose that these isoforms of NFI proteins might provide a molecular basis for skeletal muscle diversity.
Spitz
F
F
Institut Cochin de Génétique Moléculaire, INSERM U129, Université René Descartes, Paris, France.
Salminen
M
M
Demignon
J
J
Kahn
A
A
Daegelen
D
D
Maire
P
P
D000818:Animals; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D005091:Exons; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D064326:MEF2 Transcription Factors; D051379:Mice; D008822:Mice, Transgenic; D018656:Muscle Fibers, Fast-Twitch / Q000737:chemistry / Q000502:physiology*; D018006:Myogenic Regulatory Factors; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C111931:ELF4 protein, human; C491779:Elf4 protein, mouse; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C486169:Ybx1 protein, rat; D005634:Fructose-Bisphosphate Aldolase