A temporal map of transcription factor activity: mef2 directly regulates target genes at all stages of muscle development.
Dissecting components of key transcriptional networks is essential for understanding complex developmental processes and phenotypes. Genetic studies have highlighted the role of members of the Mef2 family of transcription factors as essential regulators in myogenesis from flies to man. To understand how these transcription factors control diverse processes in muscle development, we have combined chromatin immunoprecipitation analysis with gene expression profiling to obtain a temporal map of Mef2 activity during Drosophila embryonic development. This global approach revealed three temporal patterns of Mef2 enhancer binding, providing a glimpse of dynamic enhancer use within the context of a developing embryo. Our results provide mechanistic insight into the regulation of Mef2's activity at the level of DNA binding and suggest cooperativity with the bHLH protein Twist. The number and diversity of new direct target genes indicates a much broader role for Mef2, at all stages of myogenesis, than previously anticipated.
Sandmann
Thomas
T
European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.
Jensen
Lars J
LJ
Jakobsen
Janus S
JS
Karzynski
Michal M
MM
Eichenlaub
Michael P
MP
Bork
Peer
P
Furlong
Eileen E M
EE
D000818:Animals; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology; D004625:Embryo, Nonmammalian; D004742:Enhancer Elements, Genetic; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D017344:Genes, Insect; D007700:Kinetics; D008954:Models, Biological; D024510:Muscle Development / Q000502:physiology*; D009154:Mutation; D018006:Myogenic Regulatory Factors / Q000235:genetics* / Q000502:physiology; D011485:Protein Binding; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000502:physiology
D029721:Drosophila Proteins; C499409:Mef2 protein, Drosophila; D018006:Myogenic Regulatory Factors; D051879:Twist-Related Protein 1