Genome-wide analyses of Shavenbaby target genes reveals distinct features of enhancer organization
- Equal contributors
1 Centre de Biologie du Développement, Université de Toulouse, 118 route de Narbonne, Toulouse, F-31062, France
2 CNRS UMR5547, 118 route de Narbonne, Toulouse, F-31062, France
3 Laboratoire de Physique Statistique, CNRS, Université Pierre & Marie Curie, Université Denis Diderot, ENS, 24, rue Lhomond, F-75231 Paris, France
4 Current address: Department of Biology, McGill University, 845 Sherbrooke St W, Montreal, QC H3A 0G4, Canada
5 Institute for Genomics and Systems Biology, Department of Human Genetics, The University of Chicago, 57th St Room, 10100 Chicago, IL 60637, USA
6 Université de Toulouse, INSA, 118 route de Narbonne, Toulouse, F-31062, France
7 Institut de Mathématiques, CNRS UMR5219, 118 route de Narbonne, Toulouse, F-31062, France
8 Current address: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Dr., Ashburn, VA 20147, USA
9 Laboratory of Computational Biology, Center for Human Genetics KU Leuven, O&N I Herestraat 49 - 3000 Leuven, Belgium
Genome Biology 2013, 14:R86 doi:10.1186/gb-2013-14-8-r86Published: 23 August 2013
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.
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.
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.