title: Temporal ChIP-on-chip reveals Biniou as a universal regulator of the visceral muscle transcriptional network.
abstract: Smooth muscle plays a prominent role in many fundamental processes and diseases, yet our understanding of the transcriptional network regulating its development is very limited. The FoxF transcription factors are essential for visceral smooth muscle development in diverse species, although their direct regulatory role remains elusive. We present a transcriptional map of Biniou (a FoxF transcription factor) and Bagpipe (an Nkx factor) activity, as a first step to deciphering the developmental program regulating Drosophila visceral muscle development. A time course of chromatin immunoprecipitatation followed by microarray analysis (ChIP-on-chip) experiments and expression profiling of mutant embryos reveal a dynamic map of in vivo bound enhancers and direct target genes. While Biniou is broadly expressed, it regulates enhancers driving temporally and spatially restricted expression. In vivo reporter assays indicate that the timing of Biniou binding is a key trigger for the time span of enhancer activity. Although bagpipe and biniou mutants phenocopy each other, their regulatory potential is quite different. This network architecture was not apparent from genetic studies, and highlights Biniou as a universal regulator in all visceral muscle, regardless of its developmental origin or subsequent function. The regulatory connection of a number of Biniou target genes is conserved in mice, suggesting an ancient wiring of this developmental program.
authors.affiliation: European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.
authors.forename: Janus S
authors.initials: JS
authors.lastname: Jakobsen
authors.forename: Martina
authors.initials: M
authors.lastname: Braun
authors.forename: Jeanette
authors.initials: J
authors.lastname: Astorga
authors.forename: E Hilary
authors.initials: EH
authors.lastname: Gustafson
authors.forename: Thomas
authors.initials: T
authors.lastname: Sandmann
authors.forename: Michal
authors.initials: M
authors.lastname: Karzynski
authors.forename: Peter
authors.initials: P
authors.lastname: Carlsson
authors.forename: Eileen E M
authors.initials: EE
authors.lastname: Furlong
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D017124:Conserved Sequence; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D051858:Forkhead Transcription Factors; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009130:Muscle, Smooth / Q000196:embryology*; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014781:Viscera / Q000196:embryology
chemical_list: D029721:Drosophila Proteins; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D014157:Transcription Factors; C104163:bagpipe protein, Drosophila; C440017:bin protein, Drosophila