title: Coordinated repression and activation of two transcriptional programs stabilizes cell fate during myogenesis.
abstract: Molecular models of cell fate specification typically focus on the activation of specific lineage programs. However, the concurrent repression of unwanted transcriptional networks is also essential to stabilize certain cellular identities, as shown in a number of diverse systems and phyla. Here, we demonstrate that this dual requirement also holds true in the context of Drosophila myogenesis. By integrating genetics and genomics, we identified a new role for the pleiotropic transcriptional repressor Tramtrack69 in myoblast specification. Drosophila muscles are formed through the fusion of two discrete cell types: founder cells (FCs) and fusion-competent myoblasts (FCMs). When tramtrack69 is removed, FCMs appear to adopt an alternative muscle FC-like fate. Conversely, ectopic expression of this repressor phenocopies muscle defects seen in loss-of-function lame duck mutants, a transcription factor specific to FCMs. This occurs through Tramtrack69-mediated repression in FCMs, whereas Lame duck activates a largely distinct transcriptional program in the same cells. Lineage-specific factors are therefore not sufficient to maintain FCM identity. Instead, their identity appears more plastic, requiring the combination of instructive repressive and activating programs to stabilize cell fate.
authors: European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg 69117, Germany.
authors: Lucia
authors: L
authors: Ciglar
authors: European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg 69117, Germany.
authors: Charles
authors: C
authors: Girardot
authors: European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg 69117, Germany.
authors: Bartek
authors: B
authors: Wilczyński
authors: European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg 69117, Germany.
authors: Martina
authors: M
authors: Braun
authors: European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg 69117, Germany furlong@embl.de.
authors: Eileen E M
authors: EE
authors: Furlong
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D017404:In Situ Hybridization, Fluorescence; D008648:Mesoderm / Q000502:physiology; D024510:Muscle Development / Q000502:physiology*; D032446:Myoblasts / Q000378:metabolism / Q000502:physiology*; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D018006:Myogenic Regulatory Factors; D012097:Repressor Proteins; C442328:lmd protein, Drosophila; C075878:ttk protein, Drosophila
keywords: Drosophila; Enhancer; Myoblast cell fate specification; Tramtrack69; Transcriptional networks; Transcriptional repression