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...

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Published in:	Developmental cell Vol. 10; no. 6; pp. 797 - 807
Main Authors:	Sandmann, Thomas, Jensen, Lars J., Jakobsen, Janus S., Karzynski, Michal M., Eichenlaub, Michael P., Bork, Peer, Furlong, Eileen E.M.
Format:	Journal Article
Language:	English
Published:	Cambridge, MA Elsevier Inc 01-06-2006 Cell Press
Subjects:	Animals Binding Sites Biological and medical sciences Cell differentiation, maturation, development, hematopoiesis Cell physiology Chromatin Immunoprecipitation DEVBIO DNA Drosophila Drosophila - embryology Drosophila - genetics Drosophila Proteins - genetics Drosophila Proteins - physiology Embryo, Nonmammalian Enhancer Elements, Genetic Fundamental and applied biological sciences. Psychology Gene Expression Profiling Gene Expression Regulation, Developmental Gene Targeting Genes, Insect Kinetics Models, Biological Molecular and cellular biology Muscle Development - physiology Mutation Myogenic Regulatory Factors - genetics Myogenic Regulatory Factors - physiology Protein Binding SYSBIO Twist-Related Protein 1 - genetics Twist-Related Protein 1 - physiology SYSBIO DNA DEVBIO Development Regulation(control) Muscle Gene Transcription factor
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1534-5807 1878-1551
DOI:	10.1016/j.devcel.2006.04.009