title: Genome-wide analyses of Shavenbaby target genes reveals distinct features of enhancer organization.
abstract: BACKGROUND
  Developmental programs are implemented by regulatory interactions between Transcription Factors (TFs) and their target genes, which remain poorly understood. While recent studies have focused on regulatory cascades of TFs that govern early development, little is known about how the ultimate effectors of cell differentiation are selected and controlled. We addressed this question during late Drosophila embryogenesis, when the finely tuned expression of the TF Ovo/Shavenbaby (Svb) triggers the morphological differentiation of epidermal trichomes.
  
  
  RESULTS
  We defined a sizeable set of genes downstream of Svb and used in vivo assays to delineate 14 enhancers driving their specific expression in trichome cells. Coupling computational modeling to functional dissection, we investigated the regulatory logic of these enhancers. Extending the repertoire of epidermal effectors using genome-wide approaches showed that the regulatory models learned from this first sample are representative of the whole set of trichome enhancers. These enhancers harbor remarkable features with respect to their functional architectures, including a weak or non-existent clustering of Svb binding sites. The in vivo function of each site relies on its intimate context, notably the flanking nucleotides. Two additional cis-regulatory motifs, present in a broad diversity of composition and positioning among trichome enhancers, critically contribute to enhancer activity.
  
  
  CONCLUSIONS
  Our results show that Svb directly regulates a large set of terminal effectors of the remodeling of epidermal cells. Further, these data reveal that trichome formation is underpinned by unexpectedly diverse modes of regulation, providing fresh insights into the functional architecture of enhancers governing a terminal differentiation program.
authors: Delphine
authors: D
authors: Menoret
authors: Marc
authors: M
authors: Santolini
authors: Isabelle
authors: I
authors: Fernandes
authors: Rebecca
authors: R
authors: Spokony
authors: Jennifer
authors: J
authors: Zanet
authors: Ignacio
authors: I
authors: Gonzalez
authors: Yvan
authors: Y
authors: Latapie
authors: Pierre
authors: P
authors: Ferrer
authors: Hervé
authors: H
authors: Rouault
authors: Kevin P
authors: KP
authors: White
authors: Philippe
authors: P
authors: Besse
authors: Vincent
authors: V
authors: Hakim
authors: Stein
authors: S
authors: Aerts
authors: Francois
authors: F
authors: Payre
authors: Serge
authors: S
authors: Plaza
mesh_terms: D000818:Animals; D001665:Binding Sites; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D064201:Trichomes / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; C089512:ovo protein, Drosophila
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