Specific activation of the acetylcholine receptor subunit genes by MyoD family proteins.
Whether the myogenic regulatory factors (MRFs) of the MyoD family can discriminate among the muscle gene targets for the proper and reproducible formation of skeletal muscle is a recurrent question. We have previously shown that, in Xenopus laevis, myogenin specifically transactivated muscle structural genes in vivo. In the present study, we used the Xenopus model to examine the role of XMyoD, XMyf5, and XMRF4 for the transactivation of the (nicotinic acetylcholine receptor) nAChR genes in vivo. During early Xenopus development, the expression patterns of nAChR subunit genes proved to be correlated with the expression patterns of the MRFs. We show that XMyf5 specifically induced the expression of the delta-subunit gene in cap animal assays and in endoderm cells of Xenopus embryos but was unable to activate the expression of the gamma-subunit gene. In embryos, overexpression of a dominant-negative XMyf5 variant led to the repression of delta-but not gamma-subunit gene expression. Conversely, XMyoD and XMRF4 activated gamma-subunit gene expression but were unable to activate delta-subunit gene expression. Finally, all MRFs induced expression of the alpha-subunit gene. These findings strengthen the concept that one MRF can specifically control a subset of muscle genes that cannot be activated by the other MRFs.
Charbonnier
Frédéric
F
UMR 7060 CNRS, Equipe Biologie du développement et de la Différenciation Neuromusculaire, Centre Universitaire des Saints-Pères, Université René Descartes, F-75270 Paris Cedex 06, France.
Della Gaspara
Bruno
B
Armand
Anne-Sophie
AS
Lécolle
Sylvie
S
Launay
Thierry
T
Gallien
Claude-Louis
CL
Chanoine
Christophe
C
D000818:Animals; D015153:Blotting, Western; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D003720:Densitometry; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D017403:In Situ Hybridization; D009124:Muscle Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D017570:MyoD Protein / Q000378:metabolism* / Q000502:physiology*; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000737:chemistry* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015534:Trans-Activators; D014981:Xenopus; D029867:Xenopus Proteins; D014982:Xenopus laevis
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497419:Myf5 protein, Xenopus; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D015534:Trans-Activators; D029867:Xenopus Proteins; C063403:myogenic factor 6; D012313:RNA