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Citation
Aerts, S., Quan, X.J., Claeys, A., Naval Sanchez, M., Tate, P., Yan, J., Hassan, B.A. (2010). Robust Target Gene Discovery through Transcriptome Perturbations and Genome-Wide Enhancer Predictions in Drosophila Uncovers a Regulatory Basis for Sensory Specification.  PLoS Biol. 8(7): e1000435.
FlyBase ID
FBrf0211419
Publication Type
Research paper
Abstract

A comprehensive systems-level understanding of developmental programs requires the mapping of the underlying gene regulatory networks. While significant progress has been made in mapping a few such networks, almost all gene regulatory networks underlying cell-fate specification remain unknown and their discovery is significantly hampered by the paucity of generalized, in vivo validated tools of target gene and functional enhancer discovery. We combined genetic transcriptome perturbations and comprehensive computational analyses to identify a large cohort of target genes of the proneural and tumor suppressor factor Atonal, which specifies the switch from undifferentiated pluripotent cells to R8 photoreceptor neurons during larval development. Extensive in vivo validations of the predicted targets for the proneural factor Atonal demonstrate a 50% success rate of bona fide targets. Furthermore we show that these enhancers are functionally conserved by cloning orthologous enhancers from Drosophila ananassae and D. virilis in D. melanogaster. Finally, to investigate cis-regulatory cross-talk between Ato and other retinal differentiation transcription factors (TFs), we performed motif analyses and independent target predictions for Eyeless, Senseless, Suppressor of Hairless, Rough, and Glass. Our analyses show that cisTargetX identifies the correct motif from a set of coexpressed genes and accurately predicts target genes of individual TFs. The validated set of novel Ato targets exhibit functional enrichment of signaling molecules and a subset is predicted to be coregulated by other TFs within the retinal gene regulatory network.

PubMed ID
PubMed Central ID
PMC2910651 (PMC) (EuropePMC)
Related Publication(s)
Note

Whole-genome prediction of cis-regulatory modules and target genes yields insight into gene regulatory networks underlying sensory differentiation.
Aerts and Hassan, 2011, Fly 5(3): 221--223 [FBrf0250105]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    PLoS Biol.
    Title
    PLoS Biology
    Publication Year
    2003-
    ISBN/ISSN
    1545-7885 1544-9173
    Data From Reference
    Alleles (27)
    Genes (73)
    Sequence Features (14)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (4)
    Transgenic Constructs (24)