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
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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