Activation of the myogenin promoter during mouse embryogenesis in the absence of positive autoregulation.
Myogenin, a member of the MyoD family of helix-loop-helix proteins, can induce myogenesis in a wide range of cell types. In addition to activating muscle structural genes, members of the MyoD family can autoactivate their own and cross-activate one another's expression in transfected cells. This has led to the hypothesis that autoregulatory loops among these factors provide a mechanism for amplifying and maintaining the muscle-specific gene expression program in vivo. Here, we make use of myogenin-null mice to directly test this hypothesis. To investigate whether the myogenin protein autoregulates the myogenin gene during embryogenesis, we introduced a myogenin-lacZ transgene into mice harboring a null mutation at the myogenin locus. Despite a severe deficiency of skeletal muscle in myogenin-null neonates, the myogenin-lacZ transgene was expressed normally in myogenic cells throughout embryogenesis. These results show that myogenin is not required for regulation of the myogenin gene and argue against the existence of a myogenin autoregulatory loop in the embryo.
Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
T C
TC
Cheng
B S
BS
Tseng
J P
JP
Merlie
W H
WH
Klein
E N
EN
Olson
D000818:Animals; D000831:Animals, Newborn / Q000033:anatomy & histology; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009132:Muscles / Q000033:anatomy & histology / Q000196:embryology*; D018008:Myogenin / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013234:Stem Cells; D014059:Tongue / Q000033:anatomy & histology / Q000196:embryology*; D001616:beta-Galactosidase / Q000235:genetics / Q000302:isolation & purification
C503801:Myog protein, mouse; D018008:Myogenin; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase