title: Selective repression of myoD transcription by v-Myc prevents terminal differentiation of quail embryo myoblasts transformed by the MC29 strain of avian myelocytomatosis virus.
abstract: We have investigated the mechanism by which expression of the v-myc oncogene interferes with the competence of primary quail myoblasts to undergo terminal differentiation. Previous studies have established that quail myoblasts transformed by myc oncogenes are severely impaired in the accumulation of mRNAs encoding the myogenic transcription factors Myf-5, MyoD and Myogenin. However, the mechanism responsible for such a repression remains largely unknown. Here we present evidence that v-Myc selectively interferes with quail myoD expression at the transcriptional level. Cis-regulatory elements involved in the auto-activation of qmyoD are specifically targeted in this unique example of transrepression by v-Myc, without the apparent participation of Myc-specific E-boxes or InR sequences. Transiently expressed v-Myc efficiently interfered with MyoD-dependent transactivation of the qmyoD regulatory elements, while the myogenin promoter was unaffected. Finally, we show that forced expression of MyoD in v-myc-transformed quail myoblasts restored myogenin expression and promoted extensive terminal differentiation. These data suggest that transcriptional repression of qmyoD is a major and rate-limiting step in the molecular pathway by which v-Myc severely inhibits terminal differentiation in myogenic cells.
authors.affiliation: Istituto Pasteur-Fondazione Cenci-Bolognetti, Dipartimento di Biologia Cellulare e dello Sviluppo, Sezione di Scienze Microbiologiche, Universita' di Roma 'La Sapienza', 00185-Roma, Italy.
authors.forename: Severina A
authors.initials: SA
authors.lastname: La Rocca
authors.forename: Serena
authors.initials: S
authors.lastname: Vannucchi
authors.forename: Monica
authors.initials: M
authors.lastname: Pompili
authors.forename: Deborah F
authors.initials: DF
authors.lastname: Pinney
authors.forename: Charles P
authors.initials: CP
authors.lastname: Emerson
authors.forename: Milena
authors.initials: M
authors.lastname: Grossi
authors.forename: Franco
authors.initials: F
authors.lastname: Tatò
mesh_terms: D001355:Alpharetrovirus / Q000472:pathogenicity; D000818:Animals; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004625:Embryo, Nonmammalian / Q000166:cytology; D020868:Gene Silencing; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism / Q000821:virology*; D017570:MyoD Protein / Q000096:biosynthesis / Q000235:genetics*; D016274:Oncogene Protein p55(v-myc) / Q000494:pharmacology*; D011784:Quail; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic
chemical_list: D017570:MyoD Protein; D016274:Oncogene Protein p55(v-myc); D012333:RNA, Messenger