The myogenic repressor gene Holes in muscles is a direct transcriptional target of Twist and Tinman in the Drosophila embryonic mesoderm
Autor: | Richard M. Cripps, Jennifer A. Elwell, TyAnna L. Lovato, Erica M. Baca, Thai Lee, Melanie M. Adams |
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Rok vydání: | 2015 |
Předmět: |
Mef2
Mesoderm Embryo Nonmammalian animal structures Transcription Genetic Molecular Sequence Data Regulatory Sequences Nucleic Acid Biology Muscle Development Article 03 medical and health sciences Transcriptional regulation 0302 clinical medicine medicine Animals Drosophila Proteins Myocytes Cardiac Amino Acid Sequence Twist Enhancer Molecular Biology 030304 developmental biology 0303 health sciences Tinman Myogenesis Twist-Related Protein 1 Gene Expression Regulation Developmental Cell Biology Regulatory network Embryonic stem cell Molecular biology Repressor Proteins Drosophila melanogaster medicine.anatomical_structure Myogenic Regulatory Factors embryonic structures Trans-Activators Homeobox Drosophila Ectopic expression Myocyte enhancer factor-2 MEF2 Sequence Alignment 030217 neurology & neurosurgery Developmental Biology |
Zdroj: | Developmental Biology. 400:266-276 |
ISSN: | 0012-1606 |
Popis: | Understanding the regulatory circuitry controlling myogenesis is critical to understanding developmental mechanisms and developmentally-derived diseases. We analyzed the transcriptional regulation of a Drosophila myogenic repressor gene, Holes in muscles (Him). Previously, Him was shown to inhibit Myocyte enhancer factor-2 (MEF2) activity, and is expressed in myoblasts but not differentiating myotubes. We demonstrate that different phases of Him embryonic expression arise through the actions of different enhancers, and we characterize the enhancer required for its early mesoderm expression. This Him early mesoderm enhancer contains two conserved binding sites for the basic helix-loop-helix regulator Twist, and one binding site for the NK homeodomain protein Tinman. The sites for both proteins are required for enhancer activity in early embryos. Twist and Tinman activate the enhancer in tissue culture assays, and ectopic expression of either factor is sufficient to direct ectopic expression of a Him-lacZ reporter, or of the endogenous Him gene. Moreover, sustained expression of twist expression in the mesoderm up-regulates mesodermal Him expression in late embryos. Our findings provide a model to define mechanistically how Twist can both promotes myogenesis through direct activation of Mef2, and can place a brake on myogenesis, through direct activation of Him. |
Databáze: | OpenAIRE |
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