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. Thi...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1995-01, Vol.92 (2), p.561-565
Main Authors: Cheng, Tse-Chang, Tseng, Brian S., Merlie, John P., Klein, William H., Olson, Eric N.
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn - anatomy & histology
beta-Galactosidase - genetics
beta-Galactosidase - isolation & purification
Embryo, Mammalian - anatomy & histology
Embryogenesis
Embryos
Female
Gene Expression Regulation
Genes
Genes, Reporter
Genetic mutation
Genotypes
Limb buds
Male
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
Muscle development
Muscle fibers
Muscles - anatomy & histology
Muscles - embryology
Myogenin - biosynthesis
Myogenin - genetics
Prenatal development
Promoter Regions, Genetic
Proteins
Recombinant Fusion Proteins - biosynthesis
Rodents
Skeletal muscle
Stem Cells
Tongue - anatomy & histology
Tongue - embryology
Transgenes
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Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.92.2.561